Sherry Boschert

SAN FRANCISCO — The identification of 14 new target antigens and autoantibody markers for rheumatoid arthritis could help improve early diagnosis, especially in patients who are negative for conventional markers of the disease.

Eleven novel antigen-antibody systems that are specific to rheumatoid arthritis and three that are associated with the disease were identified by applying an autoantibody-profiling procedure based on cDNA phage display to clones of synovial tissue from 92 patients with rheumatoid arthritis (RA), 30 rheumatic controls, and 38 healthy controls, Klaartje Somers reported at the annual meeting of the Federation of Clinical Immunology Societies.

Combining the 11 RA-specific antigen clones into a panel produced 100% specificity and 37% sensitivity for diagnosis. Using all 14 antigen clones in a panel decreased the specificity to 85% but increased sensitivity to 53%. By deleting one of the RA-associated antigen clones and using the other 13 markers, specificity improved to 90% and the sensitivity remained at 53%, said Ms. Somers of Hasselt (Belgium) University, Diepenbeek.

Individually, 9 of 14 clones produced antibody reactivity significant enough to discriminate between RA patients and controls, according to results of receiver operating characteristic analyses.

“Very interesting” findings emerged when the panel of 14 target antigens was applied to cloned synovial fluid from 31 patients with RA who were negative for one or two conventional markers of the disease—rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies (ACPA), she said. Among these patients, 17 (55%) produced antibodies against the panel of 14 antigens.

Combining the panel's results with testing for rheumatoid factor and ACPA increased the sensitivity for diagnosis of RA, she added. In general, about a third of patients with established RA and a higher proportion with early RA will be negative for rheumatoid factor and/or ACPA. In the current study, a positive test for rheumatoid factor and/or ACPA carried a 54% sensitivity in detecting RA.

The sensitivity for diagnosis increased to 71% with testing for the two conventional markers plus applying the 11-clone panel of novel RA-specific antigens, and increased further (to 79%) with testing for the two conventional markers plus the 14-clone panel of new markers, Ms. Somers and her associates reported.

Three of the clones showed exclusive immunoreactivity in RA patients who were negative for rheumatoid factor and ACPA, who may represent a subset of all patients with RA, she said.

Antibodies to the new target antigens could be detected in early-phase RA and were significantly associated with higher levels of C-reactive protein (indicative of greater inflammation) both at the first sampling and in follow-up samples.

Preliminary immunohistochemical testing for individual novel antigens on some of the initial synovial tissue samples produced increased staining in patients with RA but not in controls, indicating increased expression of these antigens in patients with RA. “That could be an explanation for the autoantibody production that we have identified,” she said.

The investigators reported they have taken the next step of applying the panel of antigens and associated autoantibodies in a longitudinal study of patients with undifferentiated arthritis, patients with RA, and other rheumatic controls to see if the panel can predict the develop of RA.

Further analysis of the biological relevance of the new markers could inform understanding of the disease, and perhaps help identify new therapeutic targets, said Ms. Somers, who had no conflicts of interest related to this study.

SAN FRANCISCO — The identification of 14 new target antigens and autoantibody markers for rheumatoid arthritis could help improve early diagnosis, especially in patients who are negative for conventional markers of the disease.

Eleven novel antigen-antibody systems that are specific to rheumatoid arthritis and three that are associated with the disease were identified by applying an autoantibody-profiling procedure based on cDNA phage display to clones of synovial tissue from 92 patients with rheumatoid arthritis (RA), 30 rheumatic controls, and 38 healthy controls, Klaartje Somers reported at the annual meeting of the Federation of Clinical Immunology Societies.

Combining the 11 RA-specific antigen clones into a panel produced 100% specificity and 37% sensitivity for diagnosis. Using all 14 antigen clones in a panel decreased the specificity to 85% but increased sensitivity to 53%. By deleting one of the RA-associated antigen clones and using the other 13 markers, specificity improved to 90% and the sensitivity remained at 53%, said Ms. Somers of Hasselt (Belgium) University, Diepenbeek.

Individually, 9 of 14 clones produced antibody reactivity significant enough to discriminate between RA patients and controls, according to results of receiver operating characteristic analyses.

“Very interesting” findings emerged when the panel of 14 target antigens was applied to cloned synovial fluid from 31 patients with RA who were negative for one or two conventional markers of the disease—rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies (ACPA), she said. Among these patients, 17 (55%) produced antibodies against the panel of 14 antigens.

Combining the panel's results with testing for rheumatoid factor and ACPA increased the sensitivity for diagnosis of RA, she added. In general, about a third of patients with established RA and a higher proportion with early RA will be negative for rheumatoid factor and/or ACPA. In the current study, a positive test for rheumatoid factor and/or ACPA carried a 54% sensitivity in detecting RA.

The sensitivity for diagnosis increased to 71% with testing for the two conventional markers plus applying the 11-clone panel of novel RA-specific antigens, and increased further (to 79%) with testing for the two conventional markers plus the 14-clone panel of new markers, Ms. Somers and her associates reported.

Three of the clones showed exclusive immunoreactivity in RA patients who were negative for rheumatoid factor and ACPA, who may represent a subset of all patients with RA, she said.

Antibodies to the new target antigens could be detected in early-phase RA and were significantly associated with higher levels of C-reactive protein (indicative of greater inflammation) both at the first sampling and in follow-up samples.

Preliminary immunohistochemical testing for individual novel antigens on some of the initial synovial tissue samples produced increased staining in patients with RA but not in controls, indicating increased expression of these antigens in patients with RA. “That could be an explanation for the autoantibody production that we have identified,” she said.

The investigators reported they have taken the next step of applying the panel of antigens and associated autoantibodies in a longitudinal study of patients with undifferentiated arthritis, patients with RA, and other rheumatic controls to see if the panel can predict the develop of RA.

Further analysis of the biological relevance of the new markers could inform understanding of the disease, and perhaps help identify new therapeutic targets, said Ms. Somers, who had no conflicts of interest related to this study.

SAN FRANCISCO — The identification of 14 new target antigens and autoantibody markers for rheumatoid arthritis could help improve early diagnosis, especially in patients who are negative for conventional markers of the disease.

Eleven novel antigen-antibody systems that are specific to rheumatoid arthritis and three that are associated with the disease were identified by applying an autoantibody-profiling procedure based on cDNA phage display to clones of synovial tissue from 92 patients with rheumatoid arthritis (RA), 30 rheumatic controls, and 38 healthy controls, Klaartje Somers reported at the annual meeting of the Federation of Clinical Immunology Societies.

Combining the 11 RA-specific antigen clones into a panel produced 100% specificity and 37% sensitivity for diagnosis. Using all 14 antigen clones in a panel decreased the specificity to 85% but increased sensitivity to 53%. By deleting one of the RA-associated antigen clones and using the other 13 markers, specificity improved to 90% and the sensitivity remained at 53%, said Ms. Somers of Hasselt (Belgium) University, Diepenbeek.

Individually, 9 of 14 clones produced antibody reactivity significant enough to discriminate between RA patients and controls, according to results of receiver operating characteristic analyses.

“Very interesting” findings emerged when the panel of 14 target antigens was applied to cloned synovial fluid from 31 patients with RA who were negative for one or two conventional markers of the disease—rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies (ACPA), she said. Among these patients, 17 (55%) produced antibodies against the panel of 14 antigens.

Combining the panel's results with testing for rheumatoid factor and ACPA increased the sensitivity for diagnosis of RA, she added. In general, about a third of patients with established RA and a higher proportion with early RA will be negative for rheumatoid factor and/or ACPA. In the current study, a positive test for rheumatoid factor and/or ACPA carried a 54% sensitivity in detecting RA.

The sensitivity for diagnosis increased to 71% with testing for the two conventional markers plus applying the 11-clone panel of novel RA-specific antigens, and increased further (to 79%) with testing for the two conventional markers plus the 14-clone panel of new markers, Ms. Somers and her associates reported.

Three of the clones showed exclusive immunoreactivity in RA patients who were negative for rheumatoid factor and ACPA, who may represent a subset of all patients with RA, she said.

Antibodies to the new target antigens could be detected in early-phase RA and were significantly associated with higher levels of C-reactive protein (indicative of greater inflammation) both at the first sampling and in follow-up samples.

Preliminary immunohistochemical testing for individual novel antigens on some of the initial synovial tissue samples produced increased staining in patients with RA but not in controls, indicating increased expression of these antigens in patients with RA. “That could be an explanation for the autoantibody production that we have identified,” she said.

The investigators reported they have taken the next step of applying the panel of antigens and associated autoantibodies in a longitudinal study of patients with undifferentiated arthritis, patients with RA, and other rheumatic controls to see if the panel can predict the develop of RA.

Further analysis of the biological relevance of the new markers could inform understanding of the disease, and perhaps help identify new therapeutic targets, said Ms. Somers, who had no conflicts of interest related to this study.

INDIAN WELLS, CALIF. — Elderly patients with at least four of six markers of frailty before elective major surgery were significantly more likely to die within 6 months after surgery, a prospective study of 110 subjects showed.

More than half of all operations in the United States are performed on patients older than 65 years. Including six frailty markers in geriatric preoperative assessments can help predict postoperative mortality and the need for institutional care after discharge, Dr. Thomas N. Robinson and associates reported at the annual meeting of the American Surgical Association.

“Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift from the traditional preoperative evaluation techniques,” which typically stratify risk based on a single organ system assessment, said Dr. Robinson of the University of Colorado, Denver.

“We used to only look at comorbidities, urgency of procedure, and cardiac risk stratification to determine risk. Only recently have we recognized that frailty, disability, and alterations in serum markers like albumin and hematocrit can affect the outcome,” said Dr. Michael E. Zenilman, professor and chair of surgery at the State University of New York Downstate Medical Center, Brooklyn, N.Y.

The investigators chose 12 of more than 70 frailty markers to include in assessments within 30 days before elective major surgery at the Denver Veterans Affairs Medical Center. The patients, who underwent general, thoracic, vascular, or urologic surgery, had an average age of 74 years, and 95% were men.

The assessments covered age, cognition, falls, history of depression, anemia, disability, undernutrition, and comorbidity level (based on the Charlson Index, the number of outpatient medications being used, and the American Society of Anesthesiologists score).

All patients survived surgery and postoperative care in the ICU. A total of 15% of patients died within 6 months of undergoing surgery, and 26% required institutionalization in nursing homes or other care institutions upon discharge, Dr. Robinson reported.

The six frailty markers that were significantly associated with a higher risk of 6-month mortality and discharge to institutional care were:

▸ Cognitive impairment on the Mini-Cog Test. This is a simple and validated way to test for impaired cognition or dementia.

▸ Lower albumin level. This averaged 2.93 g/dL in patients who died, compared with 3.69 g/dL in patients who survived 6 months after surgery.

▸ Increased falls. Patients who died averaged 1.6 falls in the 6 months before surgery, compared with 0.7 falls in survivors.

▸ Lower hematocrit. This was 35% in patients who died and 41% in those alive 6 months after surgery.

▸ Higher Katz disability score. This averaged 3.2 among patients who died and 4.8 among survivors.

▸ Greater burden of comorbidities. Patients who died had an average Charlson Index score of 5.1, compared with 3.1 among survivors.

Dr. Robinson and his associates stated that they have no conflicts of interest.

'Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift.'

Source DR. ROBINSON

INDIAN WELLS, CALIF. — Elderly patients with at least four of six markers of frailty before elective major surgery were significantly more likely to die within 6 months after surgery, a prospective study of 110 subjects showed.

More than half of all operations in the United States are performed on patients older than 65 years. Including six frailty markers in geriatric preoperative assessments can help predict postoperative mortality and the need for institutional care after discharge, Dr. Thomas N. Robinson and associates reported at the annual meeting of the American Surgical Association.

“Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift from the traditional preoperative evaluation techniques,” which typically stratify risk based on a single organ system assessment, said Dr. Robinson of the University of Colorado, Denver.

“We used to only look at comorbidities, urgency of procedure, and cardiac risk stratification to determine risk. Only recently have we recognized that frailty, disability, and alterations in serum markers like albumin and hematocrit can affect the outcome,” said Dr. Michael E. Zenilman, professor and chair of surgery at the State University of New York Downstate Medical Center, Brooklyn, N.Y.

The investigators chose 12 of more than 70 frailty markers to include in assessments within 30 days before elective major surgery at the Denver Veterans Affairs Medical Center. The patients, who underwent general, thoracic, vascular, or urologic surgery, had an average age of 74 years, and 95% were men.

The assessments covered age, cognition, falls, history of depression, anemia, disability, undernutrition, and comorbidity level (based on the Charlson Index, the number of outpatient medications being used, and the American Society of Anesthesiologists score).

All patients survived surgery and postoperative care in the ICU. A total of 15% of patients died within 6 months of undergoing surgery, and 26% required institutionalization in nursing homes or other care institutions upon discharge, Dr. Robinson reported.

The six frailty markers that were significantly associated with a higher risk of 6-month mortality and discharge to institutional care were:

▸ Cognitive impairment on the Mini-Cog Test. This is a simple and validated way to test for impaired cognition or dementia.

▸ Lower albumin level. This averaged 2.93 g/dL in patients who died, compared with 3.69 g/dL in patients who survived 6 months after surgery.

▸ Increased falls. Patients who died averaged 1.6 falls in the 6 months before surgery, compared with 0.7 falls in survivors.

▸ Lower hematocrit. This was 35% in patients who died and 41% in those alive 6 months after surgery.

▸ Higher Katz disability score. This averaged 3.2 among patients who died and 4.8 among survivors.

▸ Greater burden of comorbidities. Patients who died had an average Charlson Index score of 5.1, compared with 3.1 among survivors.

Dr. Robinson and his associates stated that they have no conflicts of interest.

'Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift.'

Source DR. ROBINSON

INDIAN WELLS, CALIF. — Elderly patients with at least four of six markers of frailty before elective major surgery were significantly more likely to die within 6 months after surgery, a prospective study of 110 subjects showed.

More than half of all operations in the United States are performed on patients older than 65 years. Including six frailty markers in geriatric preoperative assessments can help predict postoperative mortality and the need for institutional care after discharge, Dr. Thomas N. Robinson and associates reported at the annual meeting of the American Surgical Association.

“Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift from the traditional preoperative evaluation techniques,” which typically stratify risk based on a single organ system assessment, said Dr. Robinson of the University of Colorado, Denver.

“We used to only look at comorbidities, urgency of procedure, and cardiac risk stratification to determine risk. Only recently have we recognized that frailty, disability, and alterations in serum markers like albumin and hematocrit can affect the outcome,” said Dr. Michael E. Zenilman, professor and chair of surgery at the State University of New York Downstate Medical Center, Brooklyn, N.Y.

The investigators chose 12 of more than 70 frailty markers to include in assessments within 30 days before elective major surgery at the Denver Veterans Affairs Medical Center. The patients, who underwent general, thoracic, vascular, or urologic surgery, had an average age of 74 years, and 95% were men.

The assessments covered age, cognition, falls, history of depression, anemia, disability, undernutrition, and comorbidity level (based on the Charlson Index, the number of outpatient medications being used, and the American Society of Anesthesiologists score).

All patients survived surgery and postoperative care in the ICU. A total of 15% of patients died within 6 months of undergoing surgery, and 26% required institutionalization in nursing homes or other care institutions upon discharge, Dr. Robinson reported.

The six frailty markers that were significantly associated with a higher risk of 6-month mortality and discharge to institutional care were:

▸ Cognitive impairment on the Mini-Cog Test. This is a simple and validated way to test for impaired cognition or dementia.

▸ Lower albumin level. This averaged 2.93 g/dL in patients who died, compared with 3.69 g/dL in patients who survived 6 months after surgery.

▸ Increased falls. Patients who died averaged 1.6 falls in the 6 months before surgery, compared with 0.7 falls in survivors.

▸ Lower hematocrit. This was 35% in patients who died and 41% in those alive 6 months after surgery.

▸ Higher Katz disability score. This averaged 3.2 among patients who died and 4.8 among survivors.

▸ Greater burden of comorbidities. Patients who died had an average Charlson Index score of 5.1, compared with 3.1 among survivors.

Dr. Robinson and his associates stated that they have no conflicts of interest.

'Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift.'

Source DR. ROBINSON

SAN FRANCISCO — Bringing blood pressure levels too far down increased the risk for cardiovascular events in a post hoc analysis of data on 10,001 patients with coronary artery disease in a trial of aggressive lipid-lowering therapy.

There has been some controversy around the idea of a “J curve” relationship between blood pressure and the risk for cardiovascular events, in which a higher rate of events is seen with very low and very high blood pressure levels. Every previous study except one that looked for this phenomenon found evidence of a J curve, but it's been unclear whether the J curve exists when other cardiovascular risk factors such as LDL cholesterol levels are managed aggressively, Dr. Franz H. Messerli said at a press briefing during the annual meeting of the American Society of Hypertension.

Data for the current analysis came from the double-blind Treating to New Targets trial that randomized patients aged 35-75 years with LDL cholesterol levels below 130 mg/dL to daily cholesterol-lowering therapy with 10 or 80 mg of atorvastatin. That study found significantly reduced cardiovascular risk when LDL levels were reduced to 100 mg/dL.

The post hoc analysis revealed a J curve for blood pressure. Patients who had blood pressures below or above 130-140 mm Hg systolic or 70-80 mm Hg diastolic were at higher risk for the primary end point, a composite of death from coronary disease, nonfatal MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke.

The nadirs for safe low blood pressures were 141 mm Hg systolic and 80 mm Hg diastolic, said Dr. Messerli, director of the hypertension program at St. Luke's Roosevelt Hospital, New York, who reported the findings in a poster presentation.

“The good news is that it is a relatively shallow curve,” with mild increases in risk just below those blood pressure nadirs, Dr. Messerli said. Once blood pressure drops to 110 mm Hg systolic or 60 mm Hg diastolic or lower, however, risk for the primary cardiovascular end point tripled.

Similar J-curve relationships were found for secondary end points analyzed individually—all-cause mortality, cardiovascular mortality, nonfatal MI, or stroke.

Systolic blood pressure was a stronger predictor of all-cause mortality or cardiovascular mortality. Diastolic blood pressure was a stronger predictor of nonfatal MI. Systolic and diastolic pressures equally predicted the risk for stroke.

Lower systolic pressures were better tolerated by patients aged 65 years or younger, those who had undergone revascularization procedures, and patient with no prior coronary artery bypass graft.

Hypertensive specialists consider very low blood pressures a “relatively minor” concern, Dr. Messerli said, because most patients fail to reach blood pressure targets. However, “most of us would agree that at least with coronary artery disease and diastolic blood pressure, you have to be a bit careful” in how low to go.

Dr. Messerli offered three possible explanations for the J curve. When blood pressure is too low, the coronaries are underperfused, increasing the risk of an MI. Secondly, a lower diastolic blood pressure means that pulse pressure is high, which indicates endothelial dysfunction and stiff arteries, which can lead to morbidity and mortality. Third, patients with low blood pressure may have concomitant pathology that produces higher mortality.

The study was funded by Pfizer Inc., which markets atorvastatin. Dr. Messerli has been a consultant, adviser, or speaker for other companies that make antihypertensives, lipid-lowering drugs, or other medications, but has no relationship with Pfizer.

'The good news is that it is a relatively shallow curve.'

Source DR. MESSERLI

SAN FRANCISCO — Bringing blood pressure levels too far down increased the risk for cardiovascular events in a post hoc analysis of data on 10,001 patients with coronary artery disease in a trial of aggressive lipid-lowering therapy.

There has been some controversy around the idea of a “J curve” relationship between blood pressure and the risk for cardiovascular events, in which a higher rate of events is seen with very low and very high blood pressure levels. Every previous study except one that looked for this phenomenon found evidence of a J curve, but it's been unclear whether the J curve exists when other cardiovascular risk factors such as LDL cholesterol levels are managed aggressively, Dr. Franz H. Messerli said at a press briefing during the annual meeting of the American Society of Hypertension.

Data for the current analysis came from the double-blind Treating to New Targets trial that randomized patients aged 35-75 years with LDL cholesterol levels below 130 mg/dL to daily cholesterol-lowering therapy with 10 or 80 mg of atorvastatin. That study found significantly reduced cardiovascular risk when LDL levels were reduced to 100 mg/dL.

The post hoc analysis revealed a J curve for blood pressure. Patients who had blood pressures below or above 130-140 mm Hg systolic or 70-80 mm Hg diastolic were at higher risk for the primary end point, a composite of death from coronary disease, nonfatal MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke.

The nadirs for safe low blood pressures were 141 mm Hg systolic and 80 mm Hg diastolic, said Dr. Messerli, director of the hypertension program at St. Luke's Roosevelt Hospital, New York, who reported the findings in a poster presentation.

“The good news is that it is a relatively shallow curve,” with mild increases in risk just below those blood pressure nadirs, Dr. Messerli said. Once blood pressure drops to 110 mm Hg systolic or 60 mm Hg diastolic or lower, however, risk for the primary cardiovascular end point tripled.

Similar J-curve relationships were found for secondary end points analyzed individually—all-cause mortality, cardiovascular mortality, nonfatal MI, or stroke.

Systolic blood pressure was a stronger predictor of all-cause mortality or cardiovascular mortality. Diastolic blood pressure was a stronger predictor of nonfatal MI. Systolic and diastolic pressures equally predicted the risk for stroke.

Lower systolic pressures were better tolerated by patients aged 65 years or younger, those who had undergone revascularization procedures, and patient with no prior coronary artery bypass graft.

Hypertensive specialists consider very low blood pressures a “relatively minor” concern, Dr. Messerli said, because most patients fail to reach blood pressure targets. However, “most of us would agree that at least with coronary artery disease and diastolic blood pressure, you have to be a bit careful” in how low to go.

Dr. Messerli offered three possible explanations for the J curve. When blood pressure is too low, the coronaries are underperfused, increasing the risk of an MI. Secondly, a lower diastolic blood pressure means that pulse pressure is high, which indicates endothelial dysfunction and stiff arteries, which can lead to morbidity and mortality. Third, patients with low blood pressure may have concomitant pathology that produces higher mortality.

The study was funded by Pfizer Inc., which markets atorvastatin. Dr. Messerli has been a consultant, adviser, or speaker for other companies that make antihypertensives, lipid-lowering drugs, or other medications, but has no relationship with Pfizer.

'The good news is that it is a relatively shallow curve.'

Source DR. MESSERLI

SAN FRANCISCO — Bringing blood pressure levels too far down increased the risk for cardiovascular events in a post hoc analysis of data on 10,001 patients with coronary artery disease in a trial of aggressive lipid-lowering therapy.

There has been some controversy around the idea of a “J curve” relationship between blood pressure and the risk for cardiovascular events, in which a higher rate of events is seen with very low and very high blood pressure levels. Every previous study except one that looked for this phenomenon found evidence of a J curve, but it's been unclear whether the J curve exists when other cardiovascular risk factors such as LDL cholesterol levels are managed aggressively, Dr. Franz H. Messerli said at a press briefing during the annual meeting of the American Society of Hypertension.

Data for the current analysis came from the double-blind Treating to New Targets trial that randomized patients aged 35-75 years with LDL cholesterol levels below 130 mg/dL to daily cholesterol-lowering therapy with 10 or 80 mg of atorvastatin. That study found significantly reduced cardiovascular risk when LDL levels were reduced to 100 mg/dL.

The post hoc analysis revealed a J curve for blood pressure. Patients who had blood pressures below or above 130-140 mm Hg systolic or 70-80 mm Hg diastolic were at higher risk for the primary end point, a composite of death from coronary disease, nonfatal MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke.

The nadirs for safe low blood pressures were 141 mm Hg systolic and 80 mm Hg diastolic, said Dr. Messerli, director of the hypertension program at St. Luke's Roosevelt Hospital, New York, who reported the findings in a poster presentation.

“The good news is that it is a relatively shallow curve,” with mild increases in risk just below those blood pressure nadirs, Dr. Messerli said. Once blood pressure drops to 110 mm Hg systolic or 60 mm Hg diastolic or lower, however, risk for the primary cardiovascular end point tripled.

Similar J-curve relationships were found for secondary end points analyzed individually—all-cause mortality, cardiovascular mortality, nonfatal MI, or stroke.

Systolic blood pressure was a stronger predictor of all-cause mortality or cardiovascular mortality. Diastolic blood pressure was a stronger predictor of nonfatal MI. Systolic and diastolic pressures equally predicted the risk for stroke.

Lower systolic pressures were better tolerated by patients aged 65 years or younger, those who had undergone revascularization procedures, and patient with no prior coronary artery bypass graft.

Hypertensive specialists consider very low blood pressures a “relatively minor” concern, Dr. Messerli said, because most patients fail to reach blood pressure targets. However, “most of us would agree that at least with coronary artery disease and diastolic blood pressure, you have to be a bit careful” in how low to go.

Dr. Messerli offered three possible explanations for the J curve. When blood pressure is too low, the coronaries are underperfused, increasing the risk of an MI. Secondly, a lower diastolic blood pressure means that pulse pressure is high, which indicates endothelial dysfunction and stiff arteries, which can lead to morbidity and mortality. Third, patients with low blood pressure may have concomitant pathology that produces higher mortality.

The study was funded by Pfizer Inc., which markets atorvastatin. Dr. Messerli has been a consultant, adviser, or speaker for other companies that make antihypertensives, lipid-lowering drugs, or other medications, but has no relationship with Pfizer.

'The good news is that it is a relatively shallow curve.'

Source DR. MESSERLI

SAN FRANCISCO — Hypertension causes headaches. Treating hypertension decreases headaches. Headaches increase the risk for stroke and heart disease.

Really? Not quite, Dr. Dara G. Jamieson said at the annual meeting of the American Society of Hypertension.

The reality is more nuanced:

▸ Acute hypertension can cause headache in some cases, but chronic hypertension does not.

▸ Treating chronic hypertension possibly decreases headaches, and treating acute hypertension can decrease headaches in some cases.

▸ General headaches or migraines without aura do not increase risk for stroke or heart disease, but risks for these cardiovascular problems are increased in patients who get migraines with aura, especially in women, said Dr. Jamieson of Cornell University, Ithaca, N.Y.

She described in more detail the scenarios that clinicians need to think about in the interface between hypertension and headaches.

▸ Hypertension causing headaches. A common misconception (especially among patients) that hypertension causes headaches derives from long-standing misinterpretations of a 1913 study of 870 hypertensive patients (Arch. Intern. Med. 1913;12:755-98), she said. Epidemiologic studies in the 1980s and 1990s, however, found that baseline blood pressure measurements in 22,685 adults were not associated with the risk for headaches (including migraines). On the contrary—elevated blood pressures and pulse pressures were associated with a reduced risk of headaches.

Unlike chronic hypertension, acute hypertension can cause headaches in specific circumstances, the most common being pheochromocytoma, which presents with headache in up to 80% of cases as part of a complex of symptoms.

A recurrent, short-lasting headache has been linked with transient, paroxysmal elevations of blood pressure in patients without underlying causes of pheochromocytoma. This type of headache is thought to be caused by chronic baroreceptor failure. It is seen mainly in patients who have had radiation therapy to the neck, carotid endarterectomies, or radical neck dissections, and it responds to clonidine therapy.

▸ Hypertension plus headache. A patient with a sudden-onset neurologic deficit with some degree of headache may be having an intracerebral hemorrhage or ischemic stroke. In this case, blood pressure elevation will be out of proportion to the headache. In comparison, someone with an acute thunderclap headache and less dramatic elevation in blood pressure is more likely to be having a subarachnoid hemorrhage.

Headache can be caused by acute elevation in blood pressure due to hypertensive encephalopathy, preeclampsia, eclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), or posterior reversible encephalopathy syndrome (PRES), Dr. Jamieson said. It's important to quickly recognize and aggressively treat PRES, which has a diverse presentation and can be deadly if untreated.

▸ Treating hypertension. A meta-analysis of 94 trials suggested that all classes of antihypertensive drugs reduce the prevalence of headache, but the analysis did not address the causes of headaches (Circulation 2005;112:2301-6). Some antihypertensive drugs can cause headache, especially nitric oxide donors including amyl nitrate, isosorbide, nitroglycerin, and sodium nitroprusside.

▸ Stroke and heart disease. In the 10-year Women's Health Study, migraine with aura was associated with an increased risk for ischemic stroke, MI, cardiac revascularization, and angina. An association was not so clear for men in the 16-year Physicians' Health Study, which did not differentiate between migraines with or without aura. Migraine was associated with increased risk for MI, increased risk for ischemic stroke in men aged 40-54 years, and no increased risk for angina or cardiac revascularization.

She has been a speaker or consultant for Merck & Co. Inc., Boehringer Ingelheim, and Bayer, which make medications for headaches and/or hypertension.

SAN FRANCISCO — Hypertension causes headaches. Treating hypertension decreases headaches. Headaches increase the risk for stroke and heart disease.

Really? Not quite, Dr. Dara G. Jamieson said at the annual meeting of the American Society of Hypertension.

The reality is more nuanced:

▸ Acute hypertension can cause headache in some cases, but chronic hypertension does not.

▸ Treating chronic hypertension possibly decreases headaches, and treating acute hypertension can decrease headaches in some cases.

▸ General headaches or migraines without aura do not increase risk for stroke or heart disease, but risks for these cardiovascular problems are increased in patients who get migraines with aura, especially in women, said Dr. Jamieson of Cornell University, Ithaca, N.Y.

She described in more detail the scenarios that clinicians need to think about in the interface between hypertension and headaches.

▸ Hypertension causing headaches. A common misconception (especially among patients) that hypertension causes headaches derives from long-standing misinterpretations of a 1913 study of 870 hypertensive patients (Arch. Intern. Med. 1913;12:755-98), she said. Epidemiologic studies in the 1980s and 1990s, however, found that baseline blood pressure measurements in 22,685 adults were not associated with the risk for headaches (including migraines). On the contrary—elevated blood pressures and pulse pressures were associated with a reduced risk of headaches.

Unlike chronic hypertension, acute hypertension can cause headaches in specific circumstances, the most common being pheochromocytoma, which presents with headache in up to 80% of cases as part of a complex of symptoms.

A recurrent, short-lasting headache has been linked with transient, paroxysmal elevations of blood pressure in patients without underlying causes of pheochromocytoma. This type of headache is thought to be caused by chronic baroreceptor failure. It is seen mainly in patients who have had radiation therapy to the neck, carotid endarterectomies, or radical neck dissections, and it responds to clonidine therapy.

▸ Hypertension plus headache. A patient with a sudden-onset neurologic deficit with some degree of headache may be having an intracerebral hemorrhage or ischemic stroke. In this case, blood pressure elevation will be out of proportion to the headache. In comparison, someone with an acute thunderclap headache and less dramatic elevation in blood pressure is more likely to be having a subarachnoid hemorrhage.

Headache can be caused by acute elevation in blood pressure due to hypertensive encephalopathy, preeclampsia, eclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), or posterior reversible encephalopathy syndrome (PRES), Dr. Jamieson said. It's important to quickly recognize and aggressively treat PRES, which has a diverse presentation and can be deadly if untreated.

▸ Treating hypertension. A meta-analysis of 94 trials suggested that all classes of antihypertensive drugs reduce the prevalence of headache, but the analysis did not address the causes of headaches (Circulation 2005;112:2301-6). Some antihypertensive drugs can cause headache, especially nitric oxide donors including amyl nitrate, isosorbide, nitroglycerin, and sodium nitroprusside.

▸ Stroke and heart disease. In the 10-year Women's Health Study, migraine with aura was associated with an increased risk for ischemic stroke, MI, cardiac revascularization, and angina. An association was not so clear for men in the 16-year Physicians' Health Study, which did not differentiate between migraines with or without aura. Migraine was associated with increased risk for MI, increased risk for ischemic stroke in men aged 40-54 years, and no increased risk for angina or cardiac revascularization.

She has been a speaker or consultant for Merck & Co. Inc., Boehringer Ingelheim, and Bayer, which make medications for headaches and/or hypertension.

SAN FRANCISCO — Hypertension causes headaches. Treating hypertension decreases headaches. Headaches increase the risk for stroke and heart disease.

Really? Not quite, Dr. Dara G. Jamieson said at the annual meeting of the American Society of Hypertension.

The reality is more nuanced:

▸ Acute hypertension can cause headache in some cases, but chronic hypertension does not.

▸ Treating chronic hypertension possibly decreases headaches, and treating acute hypertension can decrease headaches in some cases.

▸ General headaches or migraines without aura do not increase risk for stroke or heart disease, but risks for these cardiovascular problems are increased in patients who get migraines with aura, especially in women, said Dr. Jamieson of Cornell University, Ithaca, N.Y.

She described in more detail the scenarios that clinicians need to think about in the interface between hypertension and headaches.

▸ Hypertension causing headaches. A common misconception (especially among patients) that hypertension causes headaches derives from long-standing misinterpretations of a 1913 study of 870 hypertensive patients (Arch. Intern. Med. 1913;12:755-98), she said. Epidemiologic studies in the 1980s and 1990s, however, found that baseline blood pressure measurements in 22,685 adults were not associated with the risk for headaches (including migraines). On the contrary—elevated blood pressures and pulse pressures were associated with a reduced risk of headaches.

Unlike chronic hypertension, acute hypertension can cause headaches in specific circumstances, the most common being pheochromocytoma, which presents with headache in up to 80% of cases as part of a complex of symptoms.

A recurrent, short-lasting headache has been linked with transient, paroxysmal elevations of blood pressure in patients without underlying causes of pheochromocytoma. This type of headache is thought to be caused by chronic baroreceptor failure. It is seen mainly in patients who have had radiation therapy to the neck, carotid endarterectomies, or radical neck dissections, and it responds to clonidine therapy.

▸ Hypertension plus headache. A patient with a sudden-onset neurologic deficit with some degree of headache may be having an intracerebral hemorrhage or ischemic stroke. In this case, blood pressure elevation will be out of proportion to the headache. In comparison, someone with an acute thunderclap headache and less dramatic elevation in blood pressure is more likely to be having a subarachnoid hemorrhage.

Headache can be caused by acute elevation in blood pressure due to hypertensive encephalopathy, preeclampsia, eclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), or posterior reversible encephalopathy syndrome (PRES), Dr. Jamieson said. It's important to quickly recognize and aggressively treat PRES, which has a diverse presentation and can be deadly if untreated.

▸ Treating hypertension. A meta-analysis of 94 trials suggested that all classes of antihypertensive drugs reduce the prevalence of headache, but the analysis did not address the causes of headaches (Circulation 2005;112:2301-6). Some antihypertensive drugs can cause headache, especially nitric oxide donors including amyl nitrate, isosorbide, nitroglycerin, and sodium nitroprusside.

▸ Stroke and heart disease. In the 10-year Women's Health Study, migraine with aura was associated with an increased risk for ischemic stroke, MI, cardiac revascularization, and angina. An association was not so clear for men in the 16-year Physicians' Health Study, which did not differentiate between migraines with or without aura. Migraine was associated with increased risk for MI, increased risk for ischemic stroke in men aged 40-54 years, and no increased risk for angina or cardiac revascularization.

She has been a speaker or consultant for Merck & Co. Inc., Boehringer Ingelheim, and Bayer, which make medications for headaches and/or hypertension.

SAN FRANCISCO — Nearly 8% of 152 patients with cutaneous lupus erythematosus had refractory disease, a prospective epidemiologic study found.

Skin lesions remained active in these patients despite aggressive medical treatment with conventional therapies, Dr. Siamak Moghadam-Kia and associates reported in a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

The investigators created an online database to describe disease characteristics and to gather longitudinal information on patients with cutaneous lupus erythematosus (CLE). The information should prove useful as biotechnology companies prepare to test new therapies for the disease, noted Dr. Siamak Moghadam-Kia of the dermatology department at the University of Pennsylvania, Philadelphia.

All adult patients with CLE who were seen from January 2007 to December 2008 at the university's cutaneous autoimmunity outpatient clinic were invited to participate in the pilot study. Their cutaneous disease was evaluated using the CLE Disease Area and Severity Index (CLASI), and at each visit patients completed the CLE-Modified Skindex-29 to assess quality of life.

Subgroups included patients with acute CLE (6%), subacute CLE (25%), chronic CLE (61%), SLE plus lupus erythematous-nonspecific skin disease (8%), and one patient (less than 1%) who had only lupus erythematosus-nonspecific skin disease. (Percentages total more than 100 because of rounding.)

Among patients whose disease was refractory to therapy, 58% had generalized chronic CLE, 17% had localized chronic CLE, and 8% had subacute CLE, with the rest in other categories, Dr. Moghadam-Kia reported.

Most participants in the study were women (82%), and most cases of refractory disease were in women. In the whole cohort, the female:male sex ratio was 8:1 in subjects with acute CLE, 5:1 in subjects with subacute CLE, and nearly 4:1 in subjects with chronic CLE.

The cohort and most subgroups included a mix of races, although the subacute CLE cohort was predominantly white. The racial profile of patients with refractory disease did not differ from race distribution in the cohort as a whole.

Patients with refractory disease were significantly more likely to have a current or prior history of smoking, compared with those whose CLE responded to treatment. Smoking may be a risk factor for refractory CLE, Dr. Moghadam-Kia suggested.

The study may be the first systemic multicenter epidemiologic study of CLE in the United States, he noted.

The investigators hope to use the database prospectively to monitor response to treatment and disease severity, to assess the feasibility of measures of disease flares, and to compare measures of skin-specific and general quality of life in patients with CLE. They also hope more clinical sites will be incorporated into the database.

The poster and the meeting program did not disclose any potential conflicts of interest for the investigators.

SAN FRANCISCO — Nearly 8% of 152 patients with cutaneous lupus erythematosus had refractory disease, a prospective epidemiologic study found.

Skin lesions remained active in these patients despite aggressive medical treatment with conventional therapies, Dr. Siamak Moghadam-Kia and associates reported in a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

The investigators created an online database to describe disease characteristics and to gather longitudinal information on patients with cutaneous lupus erythematosus (CLE). The information should prove useful as biotechnology companies prepare to test new therapies for the disease, noted Dr. Siamak Moghadam-Kia of the dermatology department at the University of Pennsylvania, Philadelphia.

All adult patients with CLE who were seen from January 2007 to December 2008 at the university's cutaneous autoimmunity outpatient clinic were invited to participate in the pilot study. Their cutaneous disease was evaluated using the CLE Disease Area and Severity Index (CLASI), and at each visit patients completed the CLE-Modified Skindex-29 to assess quality of life.

Subgroups included patients with acute CLE (6%), subacute CLE (25%), chronic CLE (61%), SLE plus lupus erythematous-nonspecific skin disease (8%), and one patient (less than 1%) who had only lupus erythematosus-nonspecific skin disease. (Percentages total more than 100 because of rounding.)

Among patients whose disease was refractory to therapy, 58% had generalized chronic CLE, 17% had localized chronic CLE, and 8% had subacute CLE, with the rest in other categories, Dr. Moghadam-Kia reported.

Most participants in the study were women (82%), and most cases of refractory disease were in women. In the whole cohort, the female:male sex ratio was 8:1 in subjects with acute CLE, 5:1 in subjects with subacute CLE, and nearly 4:1 in subjects with chronic CLE.

The cohort and most subgroups included a mix of races, although the subacute CLE cohort was predominantly white. The racial profile of patients with refractory disease did not differ from race distribution in the cohort as a whole.

Patients with refractory disease were significantly more likely to have a current or prior history of smoking, compared with those whose CLE responded to treatment. Smoking may be a risk factor for refractory CLE, Dr. Moghadam-Kia suggested.

The study may be the first systemic multicenter epidemiologic study of CLE in the United States, he noted.

The investigators hope to use the database prospectively to monitor response to treatment and disease severity, to assess the feasibility of measures of disease flares, and to compare measures of skin-specific and general quality of life in patients with CLE. They also hope more clinical sites will be incorporated into the database.

The poster and the meeting program did not disclose any potential conflicts of interest for the investigators.

SAN FRANCISCO — Nearly 8% of 152 patients with cutaneous lupus erythematosus had refractory disease, a prospective epidemiologic study found.

Skin lesions remained active in these patients despite aggressive medical treatment with conventional therapies, Dr. Siamak Moghadam-Kia and associates reported in a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

The investigators created an online database to describe disease characteristics and to gather longitudinal information on patients with cutaneous lupus erythematosus (CLE). The information should prove useful as biotechnology companies prepare to test new therapies for the disease, noted Dr. Siamak Moghadam-Kia of the dermatology department at the University of Pennsylvania, Philadelphia.

All adult patients with CLE who were seen from January 2007 to December 2008 at the university's cutaneous autoimmunity outpatient clinic were invited to participate in the pilot study. Their cutaneous disease was evaluated using the CLE Disease Area and Severity Index (CLASI), and at each visit patients completed the CLE-Modified Skindex-29 to assess quality of life.

Subgroups included patients with acute CLE (6%), subacute CLE (25%), chronic CLE (61%), SLE plus lupus erythematous-nonspecific skin disease (8%), and one patient (less than 1%) who had only lupus erythematosus-nonspecific skin disease. (Percentages total more than 100 because of rounding.)

Among patients whose disease was refractory to therapy, 58% had generalized chronic CLE, 17% had localized chronic CLE, and 8% had subacute CLE, with the rest in other categories, Dr. Moghadam-Kia reported.

Most participants in the study were women (82%), and most cases of refractory disease were in women. In the whole cohort, the female:male sex ratio was 8:1 in subjects with acute CLE, 5:1 in subjects with subacute CLE, and nearly 4:1 in subjects with chronic CLE.

The cohort and most subgroups included a mix of races, although the subacute CLE cohort was predominantly white. The racial profile of patients with refractory disease did not differ from race distribution in the cohort as a whole.

Patients with refractory disease were significantly more likely to have a current or prior history of smoking, compared with those whose CLE responded to treatment. Smoking may be a risk factor for refractory CLE, Dr. Moghadam-Kia suggested.

The study may be the first systemic multicenter epidemiologic study of CLE in the United States, he noted.

The investigators hope to use the database prospectively to monitor response to treatment and disease severity, to assess the feasibility of measures of disease flares, and to compare measures of skin-specific and general quality of life in patients with CLE. They also hope more clinical sites will be incorporated into the database.

The poster and the meeting program did not disclose any potential conflicts of interest for the investigators.

INDIAN WELLS, CALIF. — Severe burns in children typically stunt growth in the first 2 years after injury, but growth curves can be normalized with some dosages of recombinant human growth hormone, a prospective, double-blind study of 206 patients found.

Children with burns covering more than 40% of their total body surface area were randomized to receive placebo or one of three doses (0.05, 0.1, or 0.2 mg/kg per day) of subcutaneous recombinant human growth hormone (rhGH) or placebo starting at discharge from the hospital through 1 year after being burned.

They were examined for treatment effects at 6, 9, 12, 18, and 24 months post burn.

The 105 patients on placebo were at the 33rd percentile for growth on standard growth curves at baseline and at all follow-up time points.

Growth returned to normal in 37 patients on 0.05 mg/kg per day rhGH at the 12- and 24-month follow-ups and at all follow-up time points in 41 patients in the 0.1-mg/kg per day rhGH group, with significantly better growth, compared with the placebo group, Dr. David N. Herndon and his associates reported at the annual meeting of the American Surgical Association.

Paradoxically, 23 patients given the highest dose of rhGH (0.2 mg/kg per day) showed less growth than did the other rhGH groups—even though the highest dose produced the greatest improvements in lean body mass and in some other parameters measured, said Dr. Herndon, chief of staff at the Shriners Burn Institute and professor and chair of surgery at the University of Texas Medical Branch, both in Galveston. Dr. Ludwik K. Branski, also of the university, was the lead investigator in the study.

The limited growth on high-dose rhGH might be related to a significant decrease in bone mineral content and a significant increase in levels of osteocalcin (a marker of bone resorption) in that group, he suggested. “This may be because we did not give them enough calcium or enough vitamin D to allow the growth-potentiating effects on bone to express themselves by increased bone mineral content,” he speculated.

The few adverse events all occurred in the high-dose group: hypercalcemia in two patients and glucose intolerance in one patient that necessitated discontinuation of rhGH.

In addition to measuring growth, rhGH levels, lean body mass, bone mineral content, and osteocalcin levels, the investigators assessed levels of insulin-like growth factor body protein 3 (a mediator of growth hormone's effects), resting energy expenditure, cardiac output, percent body fat, and parathyroid levels. “The 0.1-mg/kg per day dose had salutary effects in all body systems and did not reach a dose that was dangerous in any particular group,” and thus can be recommended for extensively burned children, Dr. Herndon said.

Commenting on the study, Dr. Basil A. Pruitt Jr. cautioned that more information is needed to evaluate the findings. “Since food intake and exercise can influence lean body mass and body weight,” it would have been helpful to have daily exercise and dietary logs in the study, said Dr. Pruitt of the University of Texas Health Sciences Center, San Antonio.

Although approximately two-thirds of each group were males, it also would be helpful to compare males with males and females with females to eliminate any potential sex bias, he suggested. Dr. Herndon said that analysis will be done.

Dr. Herndon and his associates reported having no conflicts of interest related to this study.

INDIAN WELLS, CALIF. — Severe burns in children typically stunt growth in the first 2 years after injury, but growth curves can be normalized with some dosages of recombinant human growth hormone, a prospective, double-blind study of 206 patients found.

Children with burns covering more than 40% of their total body surface area were randomized to receive placebo or one of three doses (0.05, 0.1, or 0.2 mg/kg per day) of subcutaneous recombinant human growth hormone (rhGH) or placebo starting at discharge from the hospital through 1 year after being burned.

They were examined for treatment effects at 6, 9, 12, 18, and 24 months post burn.

The 105 patients on placebo were at the 33rd percentile for growth on standard growth curves at baseline and at all follow-up time points.

Growth returned to normal in 37 patients on 0.05 mg/kg per day rhGH at the 12- and 24-month follow-ups and at all follow-up time points in 41 patients in the 0.1-mg/kg per day rhGH group, with significantly better growth, compared with the placebo group, Dr. David N. Herndon and his associates reported at the annual meeting of the American Surgical Association.

Paradoxically, 23 patients given the highest dose of rhGH (0.2 mg/kg per day) showed less growth than did the other rhGH groups—even though the highest dose produced the greatest improvements in lean body mass and in some other parameters measured, said Dr. Herndon, chief of staff at the Shriners Burn Institute and professor and chair of surgery at the University of Texas Medical Branch, both in Galveston. Dr. Ludwik K. Branski, also of the university, was the lead investigator in the study.

The limited growth on high-dose rhGH might be related to a significant decrease in bone mineral content and a significant increase in levels of osteocalcin (a marker of bone resorption) in that group, he suggested. “This may be because we did not give them enough calcium or enough vitamin D to allow the growth-potentiating effects on bone to express themselves by increased bone mineral content,” he speculated.

The few adverse events all occurred in the high-dose group: hypercalcemia in two patients and glucose intolerance in one patient that necessitated discontinuation of rhGH.

In addition to measuring growth, rhGH levels, lean body mass, bone mineral content, and osteocalcin levels, the investigators assessed levels of insulin-like growth factor body protein 3 (a mediator of growth hormone's effects), resting energy expenditure, cardiac output, percent body fat, and parathyroid levels. “The 0.1-mg/kg per day dose had salutary effects in all body systems and did not reach a dose that was dangerous in any particular group,” and thus can be recommended for extensively burned children, Dr. Herndon said.

Commenting on the study, Dr. Basil A. Pruitt Jr. cautioned that more information is needed to evaluate the findings. “Since food intake and exercise can influence lean body mass and body weight,” it would have been helpful to have daily exercise and dietary logs in the study, said Dr. Pruitt of the University of Texas Health Sciences Center, San Antonio.

Although approximately two-thirds of each group were males, it also would be helpful to compare males with males and females with females to eliminate any potential sex bias, he suggested. Dr. Herndon said that analysis will be done.

Dr. Herndon and his associates reported having no conflicts of interest related to this study.

INDIAN WELLS, CALIF. — Severe burns in children typically stunt growth in the first 2 years after injury, but growth curves can be normalized with some dosages of recombinant human growth hormone, a prospective, double-blind study of 206 patients found.

Children with burns covering more than 40% of their total body surface area were randomized to receive placebo or one of three doses (0.05, 0.1, or 0.2 mg/kg per day) of subcutaneous recombinant human growth hormone (rhGH) or placebo starting at discharge from the hospital through 1 year after being burned.

They were examined for treatment effects at 6, 9, 12, 18, and 24 months post burn.

The 105 patients on placebo were at the 33rd percentile for growth on standard growth curves at baseline and at all follow-up time points.

Growth returned to normal in 37 patients on 0.05 mg/kg per day rhGH at the 12- and 24-month follow-ups and at all follow-up time points in 41 patients in the 0.1-mg/kg per day rhGH group, with significantly better growth, compared with the placebo group, Dr. David N. Herndon and his associates reported at the annual meeting of the American Surgical Association.

Paradoxically, 23 patients given the highest dose of rhGH (0.2 mg/kg per day) showed less growth than did the other rhGH groups—even though the highest dose produced the greatest improvements in lean body mass and in some other parameters measured, said Dr. Herndon, chief of staff at the Shriners Burn Institute and professor and chair of surgery at the University of Texas Medical Branch, both in Galveston. Dr. Ludwik K. Branski, also of the university, was the lead investigator in the study.

The limited growth on high-dose rhGH might be related to a significant decrease in bone mineral content and a significant increase in levels of osteocalcin (a marker of bone resorption) in that group, he suggested. “This may be because we did not give them enough calcium or enough vitamin D to allow the growth-potentiating effects on bone to express themselves by increased bone mineral content,” he speculated.

The few adverse events all occurred in the high-dose group: hypercalcemia in two patients and glucose intolerance in one patient that necessitated discontinuation of rhGH.

In addition to measuring growth, rhGH levels, lean body mass, bone mineral content, and osteocalcin levels, the investigators assessed levels of insulin-like growth factor body protein 3 (a mediator of growth hormone's effects), resting energy expenditure, cardiac output, percent body fat, and parathyroid levels. “The 0.1-mg/kg per day dose had salutary effects in all body systems and did not reach a dose that was dangerous in any particular group,” and thus can be recommended for extensively burned children, Dr. Herndon said.

Commenting on the study, Dr. Basil A. Pruitt Jr. cautioned that more information is needed to evaluate the findings. “Since food intake and exercise can influence lean body mass and body weight,” it would have been helpful to have daily exercise and dietary logs in the study, said Dr. Pruitt of the University of Texas Health Sciences Center, San Antonio.

Although approximately two-thirds of each group were males, it also would be helpful to compare males with males and females with females to eliminate any potential sex bias, he suggested. Dr. Herndon said that analysis will be done.

Dr. Herndon and his associates reported having no conflicts of interest related to this study.

SAN FRANCISCO — For left ventricular mass to be reduced in patients with hypertension, getting the blood pressure to goal is what matters, not which antihypertensives you use, according to a phase III study.

The findings challenge conventional wisdom that credits renin angiotensin-aldosterone system inhibitors with being the most effective antihypertensives for left ventricular hypertrophy (LVH) regression, followed by calcium channel blockers, then beta-blockers, then diuretics.

“It turns out that's not the case,” Dr. Alan B. Miller said at the annual meeting of the American Society of Hypertension. “It probably doesn't matter what drug you use. If you get to the blood pressure goal, good things happen—in this case, left ventricular regression, and I suspect clinical outcomes will follow,” said Dr. Miller, professor of cardiology at the University of Florida, Jacksonville.

The multicenter, double-blind study included 287 patients with class 1 or class 2 hypertension and documented left ventricular hypertrophy who were being treated with 20 mg/day of the ACE inhibitor lisinopril. Patients were randomized to adjunctive therapy with up to 80 mg/day of the nonselective beta-blocker/alpha-1 blocker carvedilol CR (Coreg), up to 100 mg/day of the beta-blocker atenolol, or up to 40 mg/day of lisinopril without beta-blockade. Some patients also required concomitant hydrochlorothiazide or hydrochlorothiazide plus amlodipine to control hypertension.

During 12 months of treatment, 73% of the carvedilol/lisinopril group, 67% of the atenolol/lisinopril group, and 79% of the high-dose lisinopril group reached recommended blood pressure goals (less than 130/80 mm Hg for the 25% of patients who had diabetes, or less than 140/90 mm Hg for other patients).

Follow-up echocardiography or cardiac MRI showed left ventricular mass regressed by a mean 6.3 g/m

The CLEVER results support the idea that “if you lower blood pressure enough, you'll regress left ventricular hypertrophy regardless of what you use,” said session moderator Dr. Marvin Moser of Yale University, New Haven, Conn.

Rates of side effects were low, as might be expected with these established medications, Dr. Miller said. Cough was somewhat more common (17%) in the high-dose lisinopril group than in the atenolol (5%) or carvedilol (9%) groups. Fatigue was more common with atenolol (17%) than in the other two groups (7% each). Headaches were reported by 12%-15% of patients.

Dr. Miller has been a consultant and speaker for GlaxoSmithKline, which markets Coreg and funded the study, and has been a speaker for AstraZeneca and received research funds from Merck. Dr. Moser reported having no conflicts of interest.

'If you get to the blood pressure goal, good things happen—in this case, left ventricular regression.' DR. MILLER

SAN FRANCISCO — For left ventricular mass to be reduced in patients with hypertension, getting the blood pressure to goal is what matters, not which antihypertensives you use, according to a phase III study.

The findings challenge conventional wisdom that credits renin angiotensin-aldosterone system inhibitors with being the most effective antihypertensives for left ventricular hypertrophy (LVH) regression, followed by calcium channel blockers, then beta-blockers, then diuretics.

“It turns out that's not the case,” Dr. Alan B. Miller said at the annual meeting of the American Society of Hypertension. “It probably doesn't matter what drug you use. If you get to the blood pressure goal, good things happen—in this case, left ventricular regression, and I suspect clinical outcomes will follow,” said Dr. Miller, professor of cardiology at the University of Florida, Jacksonville.

The multicenter, double-blind study included 287 patients with class 1 or class 2 hypertension and documented left ventricular hypertrophy who were being treated with 20 mg/day of the ACE inhibitor lisinopril. Patients were randomized to adjunctive therapy with up to 80 mg/day of the nonselective beta-blocker/alpha-1 blocker carvedilol CR (Coreg), up to 100 mg/day of the beta-blocker atenolol, or up to 40 mg/day of lisinopril without beta-blockade. Some patients also required concomitant hydrochlorothiazide or hydrochlorothiazide plus amlodipine to control hypertension.

During 12 months of treatment, 73% of the carvedilol/lisinopril group, 67% of the atenolol/lisinopril group, and 79% of the high-dose lisinopril group reached recommended blood pressure goals (less than 130/80 mm Hg for the 25% of patients who had diabetes, or less than 140/90 mm Hg for other patients).

Follow-up echocardiography or cardiac MRI showed left ventricular mass regressed by a mean 6.3 g/m

The CLEVER results support the idea that “if you lower blood pressure enough, you'll regress left ventricular hypertrophy regardless of what you use,” said session moderator Dr. Marvin Moser of Yale University, New Haven, Conn.

Rates of side effects were low, as might be expected with these established medications, Dr. Miller said. Cough was somewhat more common (17%) in the high-dose lisinopril group than in the atenolol (5%) or carvedilol (9%) groups. Fatigue was more common with atenolol (17%) than in the other two groups (7% each). Headaches were reported by 12%-15% of patients.

Dr. Miller has been a consultant and speaker for GlaxoSmithKline, which markets Coreg and funded the study, and has been a speaker for AstraZeneca and received research funds from Merck. Dr. Moser reported having no conflicts of interest.

'If you get to the blood pressure goal, good things happen—in this case, left ventricular regression.' DR. MILLER

SAN FRANCISCO — For left ventricular mass to be reduced in patients with hypertension, getting the blood pressure to goal is what matters, not which antihypertensives you use, according to a phase III study.

The findings challenge conventional wisdom that credits renin angiotensin-aldosterone system inhibitors with being the most effective antihypertensives for left ventricular hypertrophy (LVH) regression, followed by calcium channel blockers, then beta-blockers, then diuretics.

“It turns out that's not the case,” Dr. Alan B. Miller said at the annual meeting of the American Society of Hypertension. “It probably doesn't matter what drug you use. If you get to the blood pressure goal, good things happen—in this case, left ventricular regression, and I suspect clinical outcomes will follow,” said Dr. Miller, professor of cardiology at the University of Florida, Jacksonville.

The multicenter, double-blind study included 287 patients with class 1 or class 2 hypertension and documented left ventricular hypertrophy who were being treated with 20 mg/day of the ACE inhibitor lisinopril. Patients were randomized to adjunctive therapy with up to 80 mg/day of the nonselective beta-blocker/alpha-1 blocker carvedilol CR (Coreg), up to 100 mg/day of the beta-blocker atenolol, or up to 40 mg/day of lisinopril without beta-blockade. Some patients also required concomitant hydrochlorothiazide or hydrochlorothiazide plus amlodipine to control hypertension.

During 12 months of treatment, 73% of the carvedilol/lisinopril group, 67% of the atenolol/lisinopril group, and 79% of the high-dose lisinopril group reached recommended blood pressure goals (less than 130/80 mm Hg for the 25% of patients who had diabetes, or less than 140/90 mm Hg for other patients).

Follow-up echocardiography or cardiac MRI showed left ventricular mass regressed by a mean 6.3 g/m

The CLEVER results support the idea that “if you lower blood pressure enough, you'll regress left ventricular hypertrophy regardless of what you use,” said session moderator Dr. Marvin Moser of Yale University, New Haven, Conn.

Rates of side effects were low, as might be expected with these established medications, Dr. Miller said. Cough was somewhat more common (17%) in the high-dose lisinopril group than in the atenolol (5%) or carvedilol (9%) groups. Fatigue was more common with atenolol (17%) than in the other two groups (7% each). Headaches were reported by 12%-15% of patients.

Dr. Miller has been a consultant and speaker for GlaxoSmithKline, which markets Coreg and funded the study, and has been a speaker for AstraZeneca and received research funds from Merck. Dr. Moser reported having no conflicts of interest.

'If you get to the blood pressure goal, good things happen—in this case, left ventricular regression.' DR. MILLER

SAN FRANCISCO — Bringing blood pressure levels too far down increased the risk for cardiovascular events in a post hoc analysis of data on 10,001 patients with coronary artery disease in a trial of aggressive lipid-lowering therapy.

There has been some controversy around the idea of a “J curve” relationship between blood pressure and the risk for cardiovascular events, in which a higher rate of events is seen with very low and very high blood pressure levels. Every previous study, except one that looked for this phenomenon, found evidence of a J curve, but it's been unclear whether the J curve exists when other cardiovascular risk factors such as LDL cholesterol levels are managed aggressively, Dr. Franz H. Messerli said in a press conference at the annual meeting of the American Society of Hypertension.

Data for the current analysis came from the double-blind Treating to New Targets trial that randomized patients aged 35-75 years with LDL cholesterol levels below 130 mg/dL to daily cholesterol-lowering therapy with 10 or 80 mg of atorvastatin. That study found significantly reduced cardiovascular risk when LDL levels were reduced to 100 mg/dL.

The post hoc analysis revealed a J curve for blood pressure. Patients with blood pressures below or above 130-140 mm Hg systolic or 70-80 mm Hg diastolic were at higher risk for the primary end point, a composite of death from coronary disease, nonfatal MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke.

The nadirs for safe low blood pressures were 141 mm Hg systolic and 80 mm Hg diastolic, Dr. Messerli, director of the hypertension program at St. Luke's Roosevelt Hospital, New York, said in a poster presentation. The study's lead investigator was Dr. Sripal Bangalore of Harvard Medical School, Boston.

“The good news is that it is a relatively shallow curve,” with mild increases in risk just below those blood pressure nadirs, Dr. Messerli said. But once blood pressure drops to 110 mm Hg systolic or 60 mm Hg diastolic or lower, risk for the primary cardiovascular end point tripled.

Similar J-curve relationships were found for secondary end points analyzed individually—all-cause mortality, cardiovascular mortality, nonfatal MI, or stroke.

Systolic blood pressure was a stronger predictor of all-cause mortality or cardiovascular mortality. Diastolic blood pressure was a stronger predictor of nonfatal MI. Systolic and diastolic pressures equally predicted the risk for stroke.

All patients in the study had coronary artery disease. Lower systolic pressures were better tolerated by patients aged 65 or younger, those who had undergone revascularization procedures, and those with no prior coronary artery bypass graft. The relationship between blood pressure and cardiovascular risk was not affected by gender, diabetes, heart failure, or prior MI.

Hypertensive specialists consider very low blood pressures a “relatively minor” concern, Dr. Messerli said, because most patients fail to reach blood pressure targets. However, “most of us would agree that at least with coronary artery disease and diastolic blood pressure, you have to be a bit careful” in how low to go.

Dr. William B. White of the University of Connecticut, Farmington, who moderated the press conference, said that as a hypertension specialist at a cardiology center, he sees patients who have blood pressures around 102/60 mm Hg on routine visits. “That's the message here—that this does happen in real-life practice,” he said.

If patients with these low pressures report dizziness or fatigue, he may adjust therapy to let blood pressures rise 10-12 mm Hg. “They'll probably be just as protected but have more energy and less risk of underperfusing their coronary circulation,” he said.

Dr. Messerli offered three possible explanations for the J curve. When blood pressure is too low, the coronaries are underperfused, increasing the risk of an MI. Secondly, a lower diastolic blood pressure means that pulse pressure is high, which indicates endothelial dysfunction and stiff arteries, which can lead to morbidity and mortality. Third, patients with low blood pressure may have concomitant pathology that produces higher mortality.

The study was funded by Pfizer Inc., which markets atorvastatin. Dr. Messerli has been a consultant, adviser, or speaker for companies that make antihypertensives and lipid-lowering drugs, but has no relationship with Pfizer.

'With coronary artery disease and diastolic blood pressure, you have to be a bit careful' in how low to go. DR. MESSERLI

SAN FRANCISCO — Bringing blood pressure levels too far down increased the risk for cardiovascular events in a post hoc analysis of data on 10,001 patients with coronary artery disease in a trial of aggressive lipid-lowering therapy.

There has been some controversy around the idea of a “J curve” relationship between blood pressure and the risk for cardiovascular events, in which a higher rate of events is seen with very low and very high blood pressure levels. Every previous study, except one that looked for this phenomenon, found evidence of a J curve, but it's been unclear whether the J curve exists when other cardiovascular risk factors such as LDL cholesterol levels are managed aggressively, Dr. Franz H. Messerli said in a press conference at the annual meeting of the American Society of Hypertension.

Data for the current analysis came from the double-blind Treating to New Targets trial that randomized patients aged 35-75 years with LDL cholesterol levels below 130 mg/dL to daily cholesterol-lowering therapy with 10 or 80 mg of atorvastatin. That study found significantly reduced cardiovascular risk when LDL levels were reduced to 100 mg/dL.

The post hoc analysis revealed a J curve for blood pressure. Patients with blood pressures below or above 130-140 mm Hg systolic or 70-80 mm Hg diastolic were at higher risk for the primary end point, a composite of death from coronary disease, nonfatal MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke.

The nadirs for safe low blood pressures were 141 mm Hg systolic and 80 mm Hg diastolic, Dr. Messerli, director of the hypertension program at St. Luke's Roosevelt Hospital, New York, said in a poster presentation. The study's lead investigator was Dr. Sripal Bangalore of Harvard Medical School, Boston.

“The good news is that it is a relatively shallow curve,” with mild increases in risk just below those blood pressure nadirs, Dr. Messerli said. But once blood pressure drops to 110 mm Hg systolic or 60 mm Hg diastolic or lower, risk for the primary cardiovascular end point tripled.

Similar J-curve relationships were found for secondary end points analyzed individually—all-cause mortality, cardiovascular mortality, nonfatal MI, or stroke.

Systolic blood pressure was a stronger predictor of all-cause mortality or cardiovascular mortality. Diastolic blood pressure was a stronger predictor of nonfatal MI. Systolic and diastolic pressures equally predicted the risk for stroke.

All patients in the study had coronary artery disease. Lower systolic pressures were better tolerated by patients aged 65 or younger, those who had undergone revascularization procedures, and those with no prior coronary artery bypass graft. The relationship between blood pressure and cardiovascular risk was not affected by gender, diabetes, heart failure, or prior MI.

Hypertensive specialists consider very low blood pressures a “relatively minor” concern, Dr. Messerli said, because most patients fail to reach blood pressure targets. However, “most of us would agree that at least with coronary artery disease and diastolic blood pressure, you have to be a bit careful” in how low to go.

Dr. William B. White of the University of Connecticut, Farmington, who moderated the press conference, said that as a hypertension specialist at a cardiology center, he sees patients who have blood pressures around 102/60 mm Hg on routine visits. “That's the message here—that this does happen in real-life practice,” he said.

If patients with these low pressures report dizziness or fatigue, he may adjust therapy to let blood pressures rise 10-12 mm Hg. “They'll probably be just as protected but have more energy and less risk of underperfusing their coronary circulation,” he said.

Dr. Messerli offered three possible explanations for the J curve. When blood pressure is too low, the coronaries are underperfused, increasing the risk of an MI. Secondly, a lower diastolic blood pressure means that pulse pressure is high, which indicates endothelial dysfunction and stiff arteries, which can lead to morbidity and mortality. Third, patients with low blood pressure may have concomitant pathology that produces higher mortality.

The study was funded by Pfizer Inc., which markets atorvastatin. Dr. Messerli has been a consultant, adviser, or speaker for companies that make antihypertensives and lipid-lowering drugs, but has no relationship with Pfizer.

'With coronary artery disease and diastolic blood pressure, you have to be a bit careful' in how low to go. DR. MESSERLI

SAN FRANCISCO — Bringing blood pressure levels too far down increased the risk for cardiovascular events in a post hoc analysis of data on 10,001 patients with coronary artery disease in a trial of aggressive lipid-lowering therapy.

There has been some controversy around the idea of a “J curve” relationship between blood pressure and the risk for cardiovascular events, in which a higher rate of events is seen with very low and very high blood pressure levels. Every previous study, except one that looked for this phenomenon, found evidence of a J curve, but it's been unclear whether the J curve exists when other cardiovascular risk factors such as LDL cholesterol levels are managed aggressively, Dr. Franz H. Messerli said in a press conference at the annual meeting of the American Society of Hypertension.

Data for the current analysis came from the double-blind Treating to New Targets trial that randomized patients aged 35-75 years with LDL cholesterol levels below 130 mg/dL to daily cholesterol-lowering therapy with 10 or 80 mg of atorvastatin. That study found significantly reduced cardiovascular risk when LDL levels were reduced to 100 mg/dL.

The post hoc analysis revealed a J curve for blood pressure. Patients with blood pressures below or above 130-140 mm Hg systolic or 70-80 mm Hg diastolic were at higher risk for the primary end point, a composite of death from coronary disease, nonfatal MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke.

The nadirs for safe low blood pressures were 141 mm Hg systolic and 80 mm Hg diastolic, Dr. Messerli, director of the hypertension program at St. Luke's Roosevelt Hospital, New York, said in a poster presentation. The study's lead investigator was Dr. Sripal Bangalore of Harvard Medical School, Boston.

“The good news is that it is a relatively shallow curve,” with mild increases in risk just below those blood pressure nadirs, Dr. Messerli said. But once blood pressure drops to 110 mm Hg systolic or 60 mm Hg diastolic or lower, risk for the primary cardiovascular end point tripled.

Similar J-curve relationships were found for secondary end points analyzed individually—all-cause mortality, cardiovascular mortality, nonfatal MI, or stroke.

Systolic blood pressure was a stronger predictor of all-cause mortality or cardiovascular mortality. Diastolic blood pressure was a stronger predictor of nonfatal MI. Systolic and diastolic pressures equally predicted the risk for stroke.

All patients in the study had coronary artery disease. Lower systolic pressures were better tolerated by patients aged 65 or younger, those who had undergone revascularization procedures, and those with no prior coronary artery bypass graft. The relationship between blood pressure and cardiovascular risk was not affected by gender, diabetes, heart failure, or prior MI.

Hypertensive specialists consider very low blood pressures a “relatively minor” concern, Dr. Messerli said, because most patients fail to reach blood pressure targets. However, “most of us would agree that at least with coronary artery disease and diastolic blood pressure, you have to be a bit careful” in how low to go.

Dr. William B. White of the University of Connecticut, Farmington, who moderated the press conference, said that as a hypertension specialist at a cardiology center, he sees patients who have blood pressures around 102/60 mm Hg on routine visits. “That's the message here—that this does happen in real-life practice,” he said.

If patients with these low pressures report dizziness or fatigue, he may adjust therapy to let blood pressures rise 10-12 mm Hg. “They'll probably be just as protected but have more energy and less risk of underperfusing their coronary circulation,” he said.

Dr. Messerli offered three possible explanations for the J curve. When blood pressure is too low, the coronaries are underperfused, increasing the risk of an MI. Secondly, a lower diastolic blood pressure means that pulse pressure is high, which indicates endothelial dysfunction and stiff arteries, which can lead to morbidity and mortality. Third, patients with low blood pressure may have concomitant pathology that produces higher mortality.

The study was funded by Pfizer Inc., which markets atorvastatin. Dr. Messerli has been a consultant, adviser, or speaker for companies that make antihypertensives and lipid-lowering drugs, but has no relationship with Pfizer.

'With coronary artery disease and diastolic blood pressure, you have to be a bit careful' in how low to go. DR. MESSERLI

SAN FRANCISCO — To reduce left ventricular mass in patients with hypertension, getting the blood pressure to goal is what matters, not which antihypertensives you use, according to a phase III study.

The findings challenge conventional wisdom that credits renin angiotensin-aldosterone system inhibitors with being the most effective antihypertensives for left ventricular hypertrophy (LVH) regression, followed by calcium channel blockers, then beta-blockers, then diuretics.

“It turns out that's not the case,” Dr. Alan B. Miller said at the annual meeting of the American Society of Hypertension. “It probably doesn't matter what drug you use. If you get to the blood pressure goal, good things happen—in this case, left ventricular regression, and I suspect clinical outcomes will follow,” said Dr. Miller, professor of cardiology at the University of Florida, Jacksonville.

The multicenter, double-blind study included 287 patients with class 1 or class 2 hypertension and documented left ventricular hypertrophy who were being treated with 20 mg/day of the ACE inhibitor lisinopril. Patients were randomized to adjunctive therapy with up to 80 mg/day of the nonselective beta-blocker/alpha-1 blocker carvedilol CR (Coreg), up to 100 mg/day of the beta-blocker atenolol, or up to 40 mg/day of lisinopril without beta blockade. Some patients also required concomitant hydrochlorothiazide (12.5-25 mg/day) or hydrochlorothiazide plus amlodipine (5-10 mg/day) to control hypertension.

During 12 months of treatment, 73% of the carvedilol/lisinopril group, 67% of the atenolol/lisinopril group, and 79% of the high-dose lisinopril group reached recommended blood pressure goals (less than 130/80 mm Hg for the 25% of patients who had diabetes, or less than 140/90 mm Hg for other patients).

Follow-up echocardiography or cardiac MRI showed left ventricular mass regressed by a mean 6.3 g/m2 in the carvedilol/lisinopril group, 6.7 g/m2 in the atenolol/lisinopril group, and 7.9 g/m2 in the high-dose lisinopril group, the Coreg and Left Ventricular Mass Regression (CLEVER) study found. The differences between groups in baseline and follow-up blood pressures and left ventricular mass were not statistically significant.

“The main message, which is important for the practicing doctor, is to use agents that bring the blood pressure to what the guidelines recommend,” he said.

“I think this is an interesting study. The literature that claims a major difference in outcomes in left ventricular regression” depending on the choice of drug “is scattered and based upon many erroneous conclusions,” said Dr. Marvin Moser, of Yale University, New Haven, Conn. The CLEVER results support the idea that “if you lower blood pressure enough, you'll regress left ventricular hypertrophy regardless of what you use.”

Rates of side effects were low, as might be expected with these established medications, Dr. Miller said. Cough was somewhat more common (17%) in the high-dose lisinopril group than in the atenolol (5%) or carvedilol (9%) groups. Fatigue was more common with atenolol (17%) than in the other two groups (7% each). Dizziness was slightly more common with carvedilol (14%) than with atenolol (9%) or lisinopril alone (8%). Headaches were reported by 12%-15% of patients.

Dr. Miller has been a consultant and speaker for GlaxoSmithKline, which markets Coreg and funded the study. Some of his coinvestigators were employees or consultants of the company. Dr. Miller also has been a speaker for AstraZeneca, which markets atenolol, and received research funds from Merck, which markets lisinopril. Dr. Moser reported having no conflicts of interest.

'If you get to the blood pressure goal, good things happen—in this case, left ventricular regression.' DR. MILLER

SAN FRANCISCO — To reduce left ventricular mass in patients with hypertension, getting the blood pressure to goal is what matters, not which antihypertensives you use, according to a phase III study.

The findings challenge conventional wisdom that credits renin angiotensin-aldosterone system inhibitors with being the most effective antihypertensives for left ventricular hypertrophy (LVH) regression, followed by calcium channel blockers, then beta-blockers, then diuretics.

“It turns out that's not the case,” Dr. Alan B. Miller said at the annual meeting of the American Society of Hypertension. “It probably doesn't matter what drug you use. If you get to the blood pressure goal, good things happen—in this case, left ventricular regression, and I suspect clinical outcomes will follow,” said Dr. Miller, professor of cardiology at the University of Florida, Jacksonville.

The multicenter, double-blind study included 287 patients with class 1 or class 2 hypertension and documented left ventricular hypertrophy who were being treated with 20 mg/day of the ACE inhibitor lisinopril. Patients were randomized to adjunctive therapy with up to 80 mg/day of the nonselective beta-blocker/alpha-1 blocker carvedilol CR (Coreg), up to 100 mg/day of the beta-blocker atenolol, or up to 40 mg/day of lisinopril without beta blockade. Some patients also required concomitant hydrochlorothiazide (12.5-25 mg/day) or hydrochlorothiazide plus amlodipine (5-10 mg/day) to control hypertension.

During 12 months of treatment, 73% of the carvedilol/lisinopril group, 67% of the atenolol/lisinopril group, and 79% of the high-dose lisinopril group reached recommended blood pressure goals (less than 130/80 mm Hg for the 25% of patients who had diabetes, or less than 140/90 mm Hg for other patients).

Follow-up echocardiography or cardiac MRI showed left ventricular mass regressed by a mean 6.3 g/m2 in the carvedilol/lisinopril group, 6.7 g/m2 in the atenolol/lisinopril group, and 7.9 g/m2 in the high-dose lisinopril group, the Coreg and Left Ventricular Mass Regression (CLEVER) study found. The differences between groups in baseline and follow-up blood pressures and left ventricular mass were not statistically significant.

“The main message, which is important for the practicing doctor, is to use agents that bring the blood pressure to what the guidelines recommend,” he said.

“I think this is an interesting study. The literature that claims a major difference in outcomes in left ventricular regression” depending on the choice of drug “is scattered and based upon many erroneous conclusions,” said Dr. Marvin Moser, of Yale University, New Haven, Conn. The CLEVER results support the idea that “if you lower blood pressure enough, you'll regress left ventricular hypertrophy regardless of what you use.”

Rates of side effects were low, as might be expected with these established medications, Dr. Miller said. Cough was somewhat more common (17%) in the high-dose lisinopril group than in the atenolol (5%) or carvedilol (9%) groups. Fatigue was more common with atenolol (17%) than in the other two groups (7% each). Dizziness was slightly more common with carvedilol (14%) than with atenolol (9%) or lisinopril alone (8%). Headaches were reported by 12%-15% of patients.

Dr. Miller has been a consultant and speaker for GlaxoSmithKline, which markets Coreg and funded the study. Some of his coinvestigators were employees or consultants of the company. Dr. Miller also has been a speaker for AstraZeneca, which markets atenolol, and received research funds from Merck, which markets lisinopril. Dr. Moser reported having no conflicts of interest.

'If you get to the blood pressure goal, good things happen—in this case, left ventricular regression.' DR. MILLER

SAN FRANCISCO — To reduce left ventricular mass in patients with hypertension, getting the blood pressure to goal is what matters, not which antihypertensives you use, according to a phase III study.

The findings challenge conventional wisdom that credits renin angiotensin-aldosterone system inhibitors with being the most effective antihypertensives for left ventricular hypertrophy (LVH) regression, followed by calcium channel blockers, then beta-blockers, then diuretics.

“It turns out that's not the case,” Dr. Alan B. Miller said at the annual meeting of the American Society of Hypertension. “It probably doesn't matter what drug you use. If you get to the blood pressure goal, good things happen—in this case, left ventricular regression, and I suspect clinical outcomes will follow,” said Dr. Miller, professor of cardiology at the University of Florida, Jacksonville.

The multicenter, double-blind study included 287 patients with class 1 or class 2 hypertension and documented left ventricular hypertrophy who were being treated with 20 mg/day of the ACE inhibitor lisinopril. Patients were randomized to adjunctive therapy with up to 80 mg/day of the nonselective beta-blocker/alpha-1 blocker carvedilol CR (Coreg), up to 100 mg/day of the beta-blocker atenolol, or up to 40 mg/day of lisinopril without beta blockade. Some patients also required concomitant hydrochlorothiazide (12.5-25 mg/day) or hydrochlorothiazide plus amlodipine (5-10 mg/day) to control hypertension.

During 12 months of treatment, 73% of the carvedilol/lisinopril group, 67% of the atenolol/lisinopril group, and 79% of the high-dose lisinopril group reached recommended blood pressure goals (less than 130/80 mm Hg for the 25% of patients who had diabetes, or less than 140/90 mm Hg for other patients).

Follow-up echocardiography or cardiac MRI showed left ventricular mass regressed by a mean 6.3 g/m2 in the carvedilol/lisinopril group, 6.7 g/m2 in the atenolol/lisinopril group, and 7.9 g/m2 in the high-dose lisinopril group, the Coreg and Left Ventricular Mass Regression (CLEVER) study found. The differences between groups in baseline and follow-up blood pressures and left ventricular mass were not statistically significant.

“The main message, which is important for the practicing doctor, is to use agents that bring the blood pressure to what the guidelines recommend,” he said.

“I think this is an interesting study. The literature that claims a major difference in outcomes in left ventricular regression” depending on the choice of drug “is scattered and based upon many erroneous conclusions,” said Dr. Marvin Moser, of Yale University, New Haven, Conn. The CLEVER results support the idea that “if you lower blood pressure enough, you'll regress left ventricular hypertrophy regardless of what you use.”

Rates of side effects were low, as might be expected with these established medications, Dr. Miller said. Cough was somewhat more common (17%) in the high-dose lisinopril group than in the atenolol (5%) or carvedilol (9%) groups. Fatigue was more common with atenolol (17%) than in the other two groups (7% each). Dizziness was slightly more common with carvedilol (14%) than with atenolol (9%) or lisinopril alone (8%). Headaches were reported by 12%-15% of patients.

Dr. Miller has been a consultant and speaker for GlaxoSmithKline, which markets Coreg and funded the study. Some of his coinvestigators were employees or consultants of the company. Dr. Miller also has been a speaker for AstraZeneca, which markets atenolol, and received research funds from Merck, which markets lisinopril. Dr. Moser reported having no conflicts of interest.

'If you get to the blood pressure goal, good things happen—in this case, left ventricular regression.' DR. MILLER

INDIAN WELLS, CALIF. — Elderly patients with at least four of six markers of frailty before elective major surgery were significantly more likely to die within 6 months after surgery, a prospective study of 110 subjects showed.

More than half of all operations in the United States are performed on patients older than 65 years. Including six frailty markers in geriatric preoperative assessments can help predict postoperative mortality and the probability of a patient needing transfer into institutional care after discharge, Dr. Thomas N. Robinson and associates reported at the annual meeting of the American Surgical Association.

“Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift from the traditional preoperative evaluation techniques,” which typically stratify risk based on a single organ system assessment, said Dr. Robinson of the University of Colorado, Denver.

Dr. Michael E. Zenilman, also commented favorably on the frailty markers. “We used to only look at comorbidities, urgency of procedure, and cardiac risk stratification to determine risk. Only recently have we recognized that frailty, disability, and alterations in serum markers like albumin and hematocrit can affect the outcome,” said Dr. Zenilman, professor and chair of surgery at the State University of New York Downstate Medical Center, Brooklyn, N.Y.

The investigators chose 12 of more than 70 frailty markers that have been described in the medical literature to include in assessments within 30 days before elective major surgery at the Denver Veterans Affairs Medical Center. The patients, who underwent general, thoracic, vascular, or urologic surgery, had an average age of 74 years, and 95% were men.

The assessments covered age, cognition as measured by the Mini-Cog Test, the number of falls in the past 6 months, a history of depression, the presence of anemia as reflected by hematocrit, and disability as measured by the Katz Activity of Daily Living Score, which looks for dependence in bathing, grooming, or dressing. The investigators also used three assessments of undernutrition: weight loss of 10 pounds or more in the prior 6 months, body mass index, and albumin level. Three measures assessed comorbidity level: the Charlson Index, the number of outpatient medications being used, and the American Society of Anesthesiologists (ASA) score.

The investigators chose the 12 frailty markers because they could be marked on a dashboard sheet by a nurse taking vital signs. A surgeon looking at the dashboard sheet during a visit would then be able to “risk stratify the patient in an improved fashion,” Dr. Robinson said.

All patients survived surgery and postoperative care in the ICU. A total of 15% of patients died within 6 months of undergoing surgery, and 26% required institutionalization in nursing homes or other care institutions upon discharge, Dr. Robinson reported.

The six preoperative frailty markers that were significantly associated with a higher risk of 6-month mortality were:

▸ Cognitive impairment on the Mini-Cog Test. This is a simple and validated way to test for impaired cognition or dementia using a three-item recall test and a clock-drawing test.

▸ Lower albumin level. This averaged 2.93 g/dL in patients who died, compared with 3.69 g/dL in patients who survived 6 months after surgery.

▸ Increased falls. Patients who died averaged 1.6 falls in the 6 months before surgery, compared with 0.7 falls among survivors.

▸ Lower hematocrit. This was 35% in patients who died and 41% in those alive 6 months after surgery.

▸ Higher Katz disability score. This averaged 3.2 among patients who died and 4.8 among survivors.

▸ Greater burden of comorbidities. Patients who died had an average Charlson Index score of 5.1, compared with 3.1 among survivors.

The same six factors were associated with discharge to institutional care.

Dr. Robinson and associates stated that they have no conflicts of interest.

INDIAN WELLS, CALIF. — Elderly patients with at least four of six markers of frailty before elective major surgery were significantly more likely to die within 6 months after surgery, a prospective study of 110 subjects showed.

More than half of all operations in the United States are performed on patients older than 65 years. Including six frailty markers in geriatric preoperative assessments can help predict postoperative mortality and the probability of a patient needing transfer into institutional care after discharge, Dr. Thomas N. Robinson and associates reported at the annual meeting of the American Surgical Association.

“Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift from the traditional preoperative evaluation techniques,” which typically stratify risk based on a single organ system assessment, said Dr. Robinson of the University of Colorado, Denver.

Dr. Michael E. Zenilman, also commented favorably on the frailty markers. “We used to only look at comorbidities, urgency of procedure, and cardiac risk stratification to determine risk. Only recently have we recognized that frailty, disability, and alterations in serum markers like albumin and hematocrit can affect the outcome,” said Dr. Zenilman, professor and chair of surgery at the State University of New York Downstate Medical Center, Brooklyn, N.Y.

The investigators chose 12 of more than 70 frailty markers that have been described in the medical literature to include in assessments within 30 days before elective major surgery at the Denver Veterans Affairs Medical Center. The patients, who underwent general, thoracic, vascular, or urologic surgery, had an average age of 74 years, and 95% were men.

The assessments covered age, cognition as measured by the Mini-Cog Test, the number of falls in the past 6 months, a history of depression, the presence of anemia as reflected by hematocrit, and disability as measured by the Katz Activity of Daily Living Score, which looks for dependence in bathing, grooming, or dressing. The investigators also used three assessments of undernutrition: weight loss of 10 pounds or more in the prior 6 months, body mass index, and albumin level. Three measures assessed comorbidity level: the Charlson Index, the number of outpatient medications being used, and the American Society of Anesthesiologists (ASA) score.

The investigators chose the 12 frailty markers because they could be marked on a dashboard sheet by a nurse taking vital signs. A surgeon looking at the dashboard sheet during a visit would then be able to “risk stratify the patient in an improved fashion,” Dr. Robinson said.

All patients survived surgery and postoperative care in the ICU. A total of 15% of patients died within 6 months of undergoing surgery, and 26% required institutionalization in nursing homes or other care institutions upon discharge, Dr. Robinson reported.

The six preoperative frailty markers that were significantly associated with a higher risk of 6-month mortality were:

▸ Cognitive impairment on the Mini-Cog Test. This is a simple and validated way to test for impaired cognition or dementia using a three-item recall test and a clock-drawing test.

▸ Lower albumin level. This averaged 2.93 g/dL in patients who died, compared with 3.69 g/dL in patients who survived 6 months after surgery.

▸ Increased falls. Patients who died averaged 1.6 falls in the 6 months before surgery, compared with 0.7 falls among survivors.

▸ Lower hematocrit. This was 35% in patients who died and 41% in those alive 6 months after surgery.

▸ Higher Katz disability score. This averaged 3.2 among patients who died and 4.8 among survivors.

▸ Greater burden of comorbidities. Patients who died had an average Charlson Index score of 5.1, compared with 3.1 among survivors.

The same six factors were associated with discharge to institutional care.

Dr. Robinson and associates stated that they have no conflicts of interest.

INDIAN WELLS, CALIF. — Elderly patients with at least four of six markers of frailty before elective major surgery were significantly more likely to die within 6 months after surgery, a prospective study of 110 subjects showed.

More than half of all operations in the United States are performed on patients older than 65 years. Including six frailty markers in geriatric preoperative assessments can help predict postoperative mortality and the probability of a patient needing transfer into institutional care after discharge, Dr. Thomas N. Robinson and associates reported at the annual meeting of the American Surgical Association.

“Recognition of frailty markers in a preoperative assessment of geriatric patients represents a paradigm shift from the traditional preoperative evaluation techniques,” which typically stratify risk based on a single organ system assessment, said Dr. Robinson of the University of Colorado, Denver.

Dr. Michael E. Zenilman, also commented favorably on the frailty markers. “We used to only look at comorbidities, urgency of procedure, and cardiac risk stratification to determine risk. Only recently have we recognized that frailty, disability, and alterations in serum markers like albumin and hematocrit can affect the outcome,” said Dr. Zenilman, professor and chair of surgery at the State University of New York Downstate Medical Center, Brooklyn, N.Y.

The investigators chose 12 of more than 70 frailty markers that have been described in the medical literature to include in assessments within 30 days before elective major surgery at the Denver Veterans Affairs Medical Center. The patients, who underwent general, thoracic, vascular, or urologic surgery, had an average age of 74 years, and 95% were men.

The assessments covered age, cognition as measured by the Mini-Cog Test, the number of falls in the past 6 months, a history of depression, the presence of anemia as reflected by hematocrit, and disability as measured by the Katz Activity of Daily Living Score, which looks for dependence in bathing, grooming, or dressing. The investigators also used three assessments of undernutrition: weight loss of 10 pounds or more in the prior 6 months, body mass index, and albumin level. Three measures assessed comorbidity level: the Charlson Index, the number of outpatient medications being used, and the American Society of Anesthesiologists (ASA) score.

The investigators chose the 12 frailty markers because they could be marked on a dashboard sheet by a nurse taking vital signs. A surgeon looking at the dashboard sheet during a visit would then be able to “risk stratify the patient in an improved fashion,” Dr. Robinson said.

All patients survived surgery and postoperative care in the ICU. A total of 15% of patients died within 6 months of undergoing surgery, and 26% required institutionalization in nursing homes or other care institutions upon discharge, Dr. Robinson reported.

The six preoperative frailty markers that were significantly associated with a higher risk of 6-month mortality were:

▸ Cognitive impairment on the Mini-Cog Test. This is a simple and validated way to test for impaired cognition or dementia using a three-item recall test and a clock-drawing test.

▸ Lower albumin level. This averaged 2.93 g/dL in patients who died, compared with 3.69 g/dL in patients who survived 6 months after surgery.

▸ Increased falls. Patients who died averaged 1.6 falls in the 6 months before surgery, compared with 0.7 falls among survivors.

▸ Lower hematocrit. This was 35% in patients who died and 41% in those alive 6 months after surgery.

▸ Higher Katz disability score. This averaged 3.2 among patients who died and 4.8 among survivors.

▸ Greater burden of comorbidities. Patients who died had an average Charlson Index score of 5.1, compared with 3.1 among survivors.

The same six factors were associated with discharge to institutional care.

Dr. Robinson and associates stated that they have no conflicts of interest.