Bruce Jancin

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY

CHICAGO — Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren't the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women's Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek's 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the meeting.

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women's Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women's Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It's also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women's Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

Women who reported high job strain at baseline had a 90% increased risk of myocardial infarction.

Source DR. SLOPEN

CHICAGO — Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren't the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women's Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek's 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the meeting.

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women's Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women's Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It's also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women's Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

Women who reported high job strain at baseline had a 90% increased risk of myocardial infarction.

Source DR. SLOPEN

CHICAGO — Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren't the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women's Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek's 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the meeting.

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women's Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women's Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It's also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women's Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

Women who reported high job strain at baseline had a 90% increased risk of myocardial infarction.

Source DR. SLOPEN

SAN ANTONIO – Menopausal hormone therapy with estrogen plus progestin doubles a woman's risk of death from breast cancer, nearly doubles the risk of death from non–small cell lung cancer, and increases the risk of death from colorectal cancer by 54%, according to an updated analysis of the Women's Health Initiative randomized trials.

Because breast and lung cancer are the top-two causes of cancer mortality in women, these are sobering findings with important clinical implications, Dr. Rowan T. Chlebowski observed at the annual San Antonio breast cancer symposium.

The 54% increased risk of death after diagnosis of colorectal cancer in Women's Health Initiative (WHI) participants who were randomized to combined-hormone therapy rather than placebo was a trend that did not achieve statistical significance. But it is nonetheless a finding that crushes the enthusiasm that greeted an earlier WHI report of a 44% reduction in the incidence of colorectal cancer in combined-hormone therapy users after 5.6 years of follow-up (N. Engl. J. Med. 2004;350:991-1004).

“One cannot take forward the 44% relative risk reduction in colorectal cancers as being a positive finding,” said Dr. Chlebowski, professor of medicine at the University of California, Los Angeles.

Given the initial observation of fewer colorectal cancers being diagnosed in the combined-therapy arm of the WHI, investigators were quite surprised by the tumor characteristics of these cancers at time of diagnosis: The colorectal cancers arising in the combined-therapy group – although fewer in number – were much higher risk.

In all, 76% of them were pathologically staged as regional or metastatic disease, compared with 48% of colorectal cancers in women on placebo, and 59% percent of the colorectal cancers detected in combined-hormone therapy users were lymph node positive, compared with just 29% in placebo-treated controls.

The WHI consisted of two separate National Institutes of Health–funded, randomized trials that profoundly altered the management of menopausal symptoms. In the early 1990s, more than 40% of all postmenopausal women were on hormonal therapy with estrogen alone or in combination with progestin. Following the initial WHI report of multiple adverse effects of estrogen plus progestin, the popularity of hormone therapy dropped off the table.

One WHI study involved 16,608 postmenopausal women aged 50-79 years with an intact uterus who were randomized to estrogen plus progestin or to placebo for a median of 5.6 years. The other study included 10,739 postmenopausal women with prior hysterectomy who were randomized to conjugated equine estrogens alone or placebo for an average of 7.1 years.

In the examination of WHI trends for the big-three (breast, lung, and colorectal) cancers in women, there is a consistent disparity between their relatively modestly increased incidence in dual-hormone therapy users, relative to placebo, and the far larger death rates resulting from these cancers. For example, after 11 years of follow-up, the incidence of breast cancer is up by 25% in the dual-hormone therapy group, relative to placebo.

Yet the relative increase in mortality is 96%. Similarly, the incidence of non– small cell lung cancer (NSCLC) was 23% greater in women on combined-hormone therapy than in those on placebo, but the risk of death from NSCLC was 87% greater.

“The greater effect of estrogen and progestin on deaths from breast, lung, and colorectal cancer – [compared with] the effect on incidence – [suggests that] combined-hormone therapy facilitates growth and metastatic spread of established cancers, perhaps mediated by angiogenesis stimulation,” the oncologist said, adding that “in a variety of preclinical models, estrogen and progestin are potent angiogenesis stimulators.”

The investigators' initial hypothesis was that nearly all the increase in breast cancers associated with combined-hormone therapy would involve estrogen receptor–positive tumors. Not so. In fact, the new analysis – based upon 11 years of follow-up and 678 cases of breast cancer – shows that all breast cancer subtypes appear to be increased, relative to rates in the placebo arm.

For example, combined-hormone therapy was indeed associated with an adjusted 27% greater increase in estrogen receptor–positive breast cancers than with placebo in a multivariate analysis, but it was also associated with a 40% increase in estrogen receptor–negative tumors, compared with controls. Also noteworthy were the combined-therapy group's adjusted 78% increase in triple-negative cancers, the twofold increase in HER2-overexpressing tumors, and the 37% increase in HER2-negative tumors.

Nearly all the increase in lung cancer deaths associated with dual-hormone therapy resulted from NSCLC. Hormone therapy had no effect upon small cell lung cancer rates.

Among current smokers, the cumulative risk of death from lung cancer was 3.42% in those who used dual-hormone therapy for 5-plus years and 2.39% in placebo-treated controls. In other words, 1 in 100 current smokers who used estrogen plus progestin for 5-plus years experienced an otherwise-avoidable death from NSCLC.

Among past smokers, the rate was 1 in 200. These numbers are worth keeping in mind, given that today roughly 15% of U.S. women are current smokers, and 35% are past smokers, Dr. Chlebowski noted.

Turning to the results of the estrogen-alone WHI trial, he pointed out that the therapy had no impact on incidence or death rates from lung or colorectal cancer, relative to placebo, but there was a nonsignificant 20% reduction in the relative risk of breast cancer in the hormone therapy group.

This trend for a breast cancer–reduction benefit achieved significance in the nearly 4,500 study participants who were randomized to estrogen alone or placebo 5 years or more following the last menstrual period, where the hormonal therapy group enjoyed a 37% relative risk reduction. Of course, that's not how hormone therapy is ordinarily employed in clinical practice, the physician pointed out.

One audience member rose to say that the oft-quoted sharply increased risk of uterine cancer in women with an intact uterus on estrogen alone dates back to older studies using doses that were considerably higher than those available in contemporary practice, as well as older methods of patient monitoring. What about the possibility of exploring ways to provide estrogen alone to menopausal women with an intact uterus without exposing them to increased uterine cancer risk? she asked.

Dr. Chlebowski said he thinks it's certainly an appropriate research project, but he'd advise against trying it in clinical practice, given the product labeling and the malpractice lawsuit climate.

His take-home message from the expanded WHI analysis: “Even short-term use of combined-hormone therapy should be reserved for women with limiting climacteric symptoms [that are] not manageable by other means.”

In a conference-closing review of the past year's top developments in early breast cancer, Dr. Alan Coates singled out Dr. Chlebowski's presentation on the WHI results as hands-down the most important study of the year in the field of cancer epidemiology.

“As we've known before, there's a small but real increase in the incidence of breast cancer with combined-hormone replacement. The new finding is that there's a massive increase – nearly a doubling – in mortality from breast cancer.

“And the mortality increase isn't confined to breast cancer. … This disparate increase in mortality over incidence in several tumor types suggests that the estrogen and progestin [combination] is doing something to the behavior of existing tumors,” commented Dr. Coates of the University of Sydney.

It may be, as Dr. Chlebowski proposed, that the mechanism involves the angiogenic pathway, but other investigators have demonstrated that under certain circumstances, progestagens can stimulate stem cells by a paracrine RANKL (receptor-activated nuclear factor–kappaB ligand) mechanism.

This could provide an equally plausible alternative explanation, Dr. Coates said.

Dr. Chlebowski disclosed that he receives grant support from Amgen and is on the speakers bureaus for AstraZeneca and Novartis. Dr. Coates reported having no relevant financial disclosures.

SAN ANTONIO – Menopausal hormone therapy with estrogen plus progestin doubles a woman's risk of death from breast cancer, nearly doubles the risk of death from non–small cell lung cancer, and increases the risk of death from colorectal cancer by 54%, according to an updated analysis of the Women's Health Initiative randomized trials.

Because breast and lung cancer are the top-two causes of cancer mortality in women, these are sobering findings with important clinical implications, Dr. Rowan T. Chlebowski observed at the annual San Antonio breast cancer symposium.

The 54% increased risk of death after diagnosis of colorectal cancer in Women's Health Initiative (WHI) participants who were randomized to combined-hormone therapy rather than placebo was a trend that did not achieve statistical significance. But it is nonetheless a finding that crushes the enthusiasm that greeted an earlier WHI report of a 44% reduction in the incidence of colorectal cancer in combined-hormone therapy users after 5.6 years of follow-up (N. Engl. J. Med. 2004;350:991-1004).

“One cannot take forward the 44% relative risk reduction in colorectal cancers as being a positive finding,” said Dr. Chlebowski, professor of medicine at the University of California, Los Angeles.

Given the initial observation of fewer colorectal cancers being diagnosed in the combined-therapy arm of the WHI, investigators were quite surprised by the tumor characteristics of these cancers at time of diagnosis: The colorectal cancers arising in the combined-therapy group – although fewer in number – were much higher risk.

In all, 76% of them were pathologically staged as regional or metastatic disease, compared with 48% of colorectal cancers in women on placebo, and 59% percent of the colorectal cancers detected in combined-hormone therapy users were lymph node positive, compared with just 29% in placebo-treated controls.

The WHI consisted of two separate National Institutes of Health–funded, randomized trials that profoundly altered the management of menopausal symptoms. In the early 1990s, more than 40% of all postmenopausal women were on hormonal therapy with estrogen alone or in combination with progestin. Following the initial WHI report of multiple adverse effects of estrogen plus progestin, the popularity of hormone therapy dropped off the table.

One WHI study involved 16,608 postmenopausal women aged 50-79 years with an intact uterus who were randomized to estrogen plus progestin or to placebo for a median of 5.6 years. The other study included 10,739 postmenopausal women with prior hysterectomy who were randomized to conjugated equine estrogens alone or placebo for an average of 7.1 years.

In the examination of WHI trends for the big-three (breast, lung, and colorectal) cancers in women, there is a consistent disparity between their relatively modestly increased incidence in dual-hormone therapy users, relative to placebo, and the far larger death rates resulting from these cancers. For example, after 11 years of follow-up, the incidence of breast cancer is up by 25% in the dual-hormone therapy group, relative to placebo.

Yet the relative increase in mortality is 96%. Similarly, the incidence of non– small cell lung cancer (NSCLC) was 23% greater in women on combined-hormone therapy than in those on placebo, but the risk of death from NSCLC was 87% greater.

“The greater effect of estrogen and progestin on deaths from breast, lung, and colorectal cancer – [compared with] the effect on incidence – [suggests that] combined-hormone therapy facilitates growth and metastatic spread of established cancers, perhaps mediated by angiogenesis stimulation,” the oncologist said, adding that “in a variety of preclinical models, estrogen and progestin are potent angiogenesis stimulators.”

The investigators' initial hypothesis was that nearly all the increase in breast cancers associated with combined-hormone therapy would involve estrogen receptor–positive tumors. Not so. In fact, the new analysis – based upon 11 years of follow-up and 678 cases of breast cancer – shows that all breast cancer subtypes appear to be increased, relative to rates in the placebo arm.

For example, combined-hormone therapy was indeed associated with an adjusted 27% greater increase in estrogen receptor–positive breast cancers than with placebo in a multivariate analysis, but it was also associated with a 40% increase in estrogen receptor–negative tumors, compared with controls. Also noteworthy were the combined-therapy group's adjusted 78% increase in triple-negative cancers, the twofold increase in HER2-overexpressing tumors, and the 37% increase in HER2-negative tumors.

Nearly all the increase in lung cancer deaths associated with dual-hormone therapy resulted from NSCLC. Hormone therapy had no effect upon small cell lung cancer rates.

Among current smokers, the cumulative risk of death from lung cancer was 3.42% in those who used dual-hormone therapy for 5-plus years and 2.39% in placebo-treated controls. In other words, 1 in 100 current smokers who used estrogen plus progestin for 5-plus years experienced an otherwise-avoidable death from NSCLC.

Among past smokers, the rate was 1 in 200. These numbers are worth keeping in mind, given that today roughly 15% of U.S. women are current smokers, and 35% are past smokers, Dr. Chlebowski noted.

Turning to the results of the estrogen-alone WHI trial, he pointed out that the therapy had no impact on incidence or death rates from lung or colorectal cancer, relative to placebo, but there was a nonsignificant 20% reduction in the relative risk of breast cancer in the hormone therapy group.

This trend for a breast cancer–reduction benefit achieved significance in the nearly 4,500 study participants who were randomized to estrogen alone or placebo 5 years or more following the last menstrual period, where the hormonal therapy group enjoyed a 37% relative risk reduction. Of course, that's not how hormone therapy is ordinarily employed in clinical practice, the physician pointed out.

One audience member rose to say that the oft-quoted sharply increased risk of uterine cancer in women with an intact uterus on estrogen alone dates back to older studies using doses that were considerably higher than those available in contemporary practice, as well as older methods of patient monitoring. What about the possibility of exploring ways to provide estrogen alone to menopausal women with an intact uterus without exposing them to increased uterine cancer risk? she asked.

Dr. Chlebowski said he thinks it's certainly an appropriate research project, but he'd advise against trying it in clinical practice, given the product labeling and the malpractice lawsuit climate.

His take-home message from the expanded WHI analysis: “Even short-term use of combined-hormone therapy should be reserved for women with limiting climacteric symptoms [that are] not manageable by other means.”

In a conference-closing review of the past year's top developments in early breast cancer, Dr. Alan Coates singled out Dr. Chlebowski's presentation on the WHI results as hands-down the most important study of the year in the field of cancer epidemiology.

“As we've known before, there's a small but real increase in the incidence of breast cancer with combined-hormone replacement. The new finding is that there's a massive increase – nearly a doubling – in mortality from breast cancer.

“And the mortality increase isn't confined to breast cancer. … This disparate increase in mortality over incidence in several tumor types suggests that the estrogen and progestin [combination] is doing something to the behavior of existing tumors,” commented Dr. Coates of the University of Sydney.

It may be, as Dr. Chlebowski proposed, that the mechanism involves the angiogenic pathway, but other investigators have demonstrated that under certain circumstances, progestagens can stimulate stem cells by a paracrine RANKL (receptor-activated nuclear factor–kappaB ligand) mechanism.

This could provide an equally plausible alternative explanation, Dr. Coates said.

Dr. Chlebowski disclosed that he receives grant support from Amgen and is on the speakers bureaus for AstraZeneca and Novartis. Dr. Coates reported having no relevant financial disclosures.

SAN ANTONIO – Menopausal hormone therapy with estrogen plus progestin doubles a woman's risk of death from breast cancer, nearly doubles the risk of death from non–small cell lung cancer, and increases the risk of death from colorectal cancer by 54%, according to an updated analysis of the Women's Health Initiative randomized trials.

Because breast and lung cancer are the top-two causes of cancer mortality in women, these are sobering findings with important clinical implications, Dr. Rowan T. Chlebowski observed at the annual San Antonio breast cancer symposium.

The 54% increased risk of death after diagnosis of colorectal cancer in Women's Health Initiative (WHI) participants who were randomized to combined-hormone therapy rather than placebo was a trend that did not achieve statistical significance. But it is nonetheless a finding that crushes the enthusiasm that greeted an earlier WHI report of a 44% reduction in the incidence of colorectal cancer in combined-hormone therapy users after 5.6 years of follow-up (N. Engl. J. Med. 2004;350:991-1004).

“One cannot take forward the 44% relative risk reduction in colorectal cancers as being a positive finding,” said Dr. Chlebowski, professor of medicine at the University of California, Los Angeles.

Given the initial observation of fewer colorectal cancers being diagnosed in the combined-therapy arm of the WHI, investigators were quite surprised by the tumor characteristics of these cancers at time of diagnosis: The colorectal cancers arising in the combined-therapy group – although fewer in number – were much higher risk.

In all, 76% of them were pathologically staged as regional or metastatic disease, compared with 48% of colorectal cancers in women on placebo, and 59% percent of the colorectal cancers detected in combined-hormone therapy users were lymph node positive, compared with just 29% in placebo-treated controls.

The WHI consisted of two separate National Institutes of Health–funded, randomized trials that profoundly altered the management of menopausal symptoms. In the early 1990s, more than 40% of all postmenopausal women were on hormonal therapy with estrogen alone or in combination with progestin. Following the initial WHI report of multiple adverse effects of estrogen plus progestin, the popularity of hormone therapy dropped off the table.

One WHI study involved 16,608 postmenopausal women aged 50-79 years with an intact uterus who were randomized to estrogen plus progestin or to placebo for a median of 5.6 years. The other study included 10,739 postmenopausal women with prior hysterectomy who were randomized to conjugated equine estrogens alone or placebo for an average of 7.1 years.

In the examination of WHI trends for the big-three (breast, lung, and colorectal) cancers in women, there is a consistent disparity between their relatively modestly increased incidence in dual-hormone therapy users, relative to placebo, and the far larger death rates resulting from these cancers. For example, after 11 years of follow-up, the incidence of breast cancer is up by 25% in the dual-hormone therapy group, relative to placebo.

Yet the relative increase in mortality is 96%. Similarly, the incidence of non– small cell lung cancer (NSCLC) was 23% greater in women on combined-hormone therapy than in those on placebo, but the risk of death from NSCLC was 87% greater.

“The greater effect of estrogen and progestin on deaths from breast, lung, and colorectal cancer – [compared with] the effect on incidence – [suggests that] combined-hormone therapy facilitates growth and metastatic spread of established cancers, perhaps mediated by angiogenesis stimulation,” the oncologist said, adding that “in a variety of preclinical models, estrogen and progestin are potent angiogenesis stimulators.”

The investigators' initial hypothesis was that nearly all the increase in breast cancers associated with combined-hormone therapy would involve estrogen receptor–positive tumors. Not so. In fact, the new analysis – based upon 11 years of follow-up and 678 cases of breast cancer – shows that all breast cancer subtypes appear to be increased, relative to rates in the placebo arm.

For example, combined-hormone therapy was indeed associated with an adjusted 27% greater increase in estrogen receptor–positive breast cancers than with placebo in a multivariate analysis, but it was also associated with a 40% increase in estrogen receptor–negative tumors, compared with controls. Also noteworthy were the combined-therapy group's adjusted 78% increase in triple-negative cancers, the twofold increase in HER2-overexpressing tumors, and the 37% increase in HER2-negative tumors.

Nearly all the increase in lung cancer deaths associated with dual-hormone therapy resulted from NSCLC. Hormone therapy had no effect upon small cell lung cancer rates.

Among current smokers, the cumulative risk of death from lung cancer was 3.42% in those who used dual-hormone therapy for 5-plus years and 2.39% in placebo-treated controls. In other words, 1 in 100 current smokers who used estrogen plus progestin for 5-plus years experienced an otherwise-avoidable death from NSCLC.

Among past smokers, the rate was 1 in 200. These numbers are worth keeping in mind, given that today roughly 15% of U.S. women are current smokers, and 35% are past smokers, Dr. Chlebowski noted.

Turning to the results of the estrogen-alone WHI trial, he pointed out that the therapy had no impact on incidence or death rates from lung or colorectal cancer, relative to placebo, but there was a nonsignificant 20% reduction in the relative risk of breast cancer in the hormone therapy group.

This trend for a breast cancer–reduction benefit achieved significance in the nearly 4,500 study participants who were randomized to estrogen alone or placebo 5 years or more following the last menstrual period, where the hormonal therapy group enjoyed a 37% relative risk reduction. Of course, that's not how hormone therapy is ordinarily employed in clinical practice, the physician pointed out.

One audience member rose to say that the oft-quoted sharply increased risk of uterine cancer in women with an intact uterus on estrogen alone dates back to older studies using doses that were considerably higher than those available in contemporary practice, as well as older methods of patient monitoring. What about the possibility of exploring ways to provide estrogen alone to menopausal women with an intact uterus without exposing them to increased uterine cancer risk? she asked.

Dr. Chlebowski said he thinks it's certainly an appropriate research project, but he'd advise against trying it in clinical practice, given the product labeling and the malpractice lawsuit climate.

His take-home message from the expanded WHI analysis: “Even short-term use of combined-hormone therapy should be reserved for women with limiting climacteric symptoms [that are] not manageable by other means.”

In a conference-closing review of the past year's top developments in early breast cancer, Dr. Alan Coates singled out Dr. Chlebowski's presentation on the WHI results as hands-down the most important study of the year in the field of cancer epidemiology.

“As we've known before, there's a small but real increase in the incidence of breast cancer with combined-hormone replacement. The new finding is that there's a massive increase – nearly a doubling – in mortality from breast cancer.

“And the mortality increase isn't confined to breast cancer. … This disparate increase in mortality over incidence in several tumor types suggests that the estrogen and progestin [combination] is doing something to the behavior of existing tumors,” commented Dr. Coates of the University of Sydney.

It may be, as Dr. Chlebowski proposed, that the mechanism involves the angiogenic pathway, but other investigators have demonstrated that under certain circumstances, progestagens can stimulate stem cells by a paracrine RANKL (receptor-activated nuclear factor–kappaB ligand) mechanism.

This could provide an equally plausible alternative explanation, Dr. Coates said.

Dr. Chlebowski disclosed that he receives grant support from Amgen and is on the speakers bureaus for AstraZeneca and Novartis. Dr. Coates reported having no relevant financial disclosures.

CHICAGO – Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It's well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the meeting.

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

“We were surprised by this finding,” she said. “Blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites,.”

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What's needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women's Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2×2 factorial design to learn if these supplements prevent the development of these diseases over a planned 5-year follow-up.

“I'm not sure that they're going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I'm glad that we're finally having a clinical trial because this is an important question,” Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

“Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, 'We think we're helping with your bones, and we may also be helping with your heart,'” she said.

The NHANES III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

'Blacks may have an adaptive resistance to the adverse effects of low vitamin D.'

Source DR. MICHOS

CHICAGO – Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It's well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the meeting.

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

“We were surprised by this finding,” she said. “Blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites,.”

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What's needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women's Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2×2 factorial design to learn if these supplements prevent the development of these diseases over a planned 5-year follow-up.

“I'm not sure that they're going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I'm glad that we're finally having a clinical trial because this is an important question,” Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

“Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, 'We think we're helping with your bones, and we may also be helping with your heart,'” she said.

The NHANES III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

'Blacks may have an adaptive resistance to the adverse effects of low vitamin D.'

Source DR. MICHOS

CHICAGO – Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It's well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the meeting.

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

“We were surprised by this finding,” she said. “Blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites,.”

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What's needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women's Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2×2 factorial design to learn if these supplements prevent the development of these diseases over a planned 5-year follow-up.

“I'm not sure that they're going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I'm glad that we're finally having a clinical trial because this is an important question,” Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

“Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, 'We think we're helping with your bones, and we may also be helping with your heart,'” she said.

The NHANES III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

'Blacks may have an adaptive resistance to the adverse effects of low vitamin D.'

Source DR. MICHOS

CHICAGO – New American College of Cardiology/American Heart Association guidelines on cardiovascular risk assessment in asymptomatic adults may be better remembered for the tests and procedures that received a thumbs-down rather than for those endorsed for routine use.

For example, genetic testing was among the newer, often glamorous tests that have captured intense public and physician interest, yet they were classified as class III – meaning they're deemed not useful and may be harmful. In other words, don't do them in people without symptoms of heart disease.

“Genetic testing is a sexy area right now, but we didn't see it as being ready or as having shown added value,” Dr. Sidney C. Smith Jr. said in a press briefing on the new guidelines held during the meeting.

Other tests that were rated class III included advanced lipid testing with measurement of apolipoproteins and particle size and density, MRI for the detection of arterial plaque, measurement of natriuretic peptide levels, and coronary CT angiography.

“You'll hear a lot of discussion about the value of coronary CT angiography in people who come into the emergency department with chest pain, but that's a very different population,” said Dr. Smith, a member of the risk assessment guideline writing committee and immediate past chair of the ACC/AHA task force on practice guidelines.

Stress echocardiography, measures of arterial stiffness, and assessment of flow-mediated dilation also received class III status, noted Dr. Smith, professor of medicine and director of the center for cardiovascular science and medicine at the University of North Carolina, Chapel Hill.

In his Ancel Keys Memorial Lecture delivered at the AHA conference, Dr. Philip Greenland, chair of the guideline writing committee, explained that new diagnostic tests have to clear a high bar: They must show evidence of added value beyond that provided by the Framingham Risk Score or another global cardiovascular risk score plus assessment of family history, which are the only class I recommendations in the new report, meaning they should be performed in all adults.

The family history is a new class I recommendation. A positive family history under the Framingham definition is a first-generation male relative with a cardiovascular event at age 50 or younger, or by age 60 or younger in a female relative.

The new guidelines state that a global cardiovascular risk score and family history are essential for everyone, preferably starting at age 20, and should be repeated every 5 years.

For a new risk marker to be considered as useful for risk prediction, it must be shown to be a statistically independent predictor after an accounting for established risk factors. Beyond that, it must also be shown to change predictive risk sufficiently to alter recommended therapy. And then it must be shown that using the novel marker to sort patients and treat them accordingly would actually yield better clinical outcomes than if the marker had not been used, said Dr. Greenland, professor of medicine and preventive medicine at Northwestern University in Chicago.

“This is a big question for almost all of our biomarkers in cardiovascular medicine, where we can perhaps show improvement in prediction, but it's not quite so clear we can show improvement in clinical outcomes,” he said. “Generally speaking, we haven't seen much evidence of improvement of risk prediction with the new markers when you look at the whole picture. The one exception, I would say, is measurement of coronary artery calcium. I came to this as a major skeptic about coronary calcium, and only after seeing some data did I come to believe that coronary calcium might actually have clinical impact. But even with coronary calcium, I think we're too early in the evaluation process to recommend routine use beyond standard risk measurement.”

Indeed, coronary artery calcium scoring gets a class IIa recommendation (meaning it's reasonable for cardiovascular risk assessment) only in asymptomatic adults who are at intermediate risk, as defined by their global Framingham-type risk assessment, with an estimated 10%-20% risk of a cardiovascular event in the next 10 years. Coronary calcium scoring gets a lesser IIb rating (meaning it 'may be considered appropriate') in patients who are at low to intermediate risk, as defined by an estimated 6%-10% risk of an event over 10 years. In patients with less than a 6% 10-year risk, it gets a class III rating.

Investigators in MESA (Multi-Ethnic Study of Atherosclerosis) found that adding coronary artery calcium scores to standard cardiovascular risk factors improved risk discrimination from 77% to 82%, which the committee deemed clinically meaningful, Dr. Smith noted.

Measurement of C-reactive protein, another hot topic, is rated class III (no benefit) in asymptomatic adults who are defined as high-risk by the Adult Treatment Panel III standard of a greater than 20% 10-year risk. Similarly, CRP is class III in low-risk men younger than age 50 and in low-risk women younger than age 60.

However, CRP gets a class IIa recommendation as a guide to deciding on statin therapy in men aged 50 or older and in women aged 60 and older with an LDL cholesterol level of less than 130 mg/dL. It gets a class IIb recommendation in asymptomatic men and women aged 50 and 60 years, respectively, or younger.

The full 54-page guideline was released online in Circulation during the conference, and it is available at http://circ.ahajournals.org/cgi/reprint/CIR.0b013e3182051b4cv1

Dr. Smith declared having no relevant financial interests. Dr. Greenland disclosed serving as a consultant to Pfizer, General Electric, and Toshiba.

'Genetic testing is a sexy area right now, but we didn't see it as being ready or as having shown added value.'

Source DR. SMITH

CHICAGO – New American College of Cardiology/American Heart Association guidelines on cardiovascular risk assessment in asymptomatic adults may be better remembered for the tests and procedures that received a thumbs-down rather than for those endorsed for routine use.

For example, genetic testing was among the newer, often glamorous tests that have captured intense public and physician interest, yet they were classified as class III – meaning they're deemed not useful and may be harmful. In other words, don't do them in people without symptoms of heart disease.

“Genetic testing is a sexy area right now, but we didn't see it as being ready or as having shown added value,” Dr. Sidney C. Smith Jr. said in a press briefing on the new guidelines held during the meeting.

Other tests that were rated class III included advanced lipid testing with measurement of apolipoproteins and particle size and density, MRI for the detection of arterial plaque, measurement of natriuretic peptide levels, and coronary CT angiography.

“You'll hear a lot of discussion about the value of coronary CT angiography in people who come into the emergency department with chest pain, but that's a very different population,” said Dr. Smith, a member of the risk assessment guideline writing committee and immediate past chair of the ACC/AHA task force on practice guidelines.

Stress echocardiography, measures of arterial stiffness, and assessment of flow-mediated dilation also received class III status, noted Dr. Smith, professor of medicine and director of the center for cardiovascular science and medicine at the University of North Carolina, Chapel Hill.

In his Ancel Keys Memorial Lecture delivered at the AHA conference, Dr. Philip Greenland, chair of the guideline writing committee, explained that new diagnostic tests have to clear a high bar: They must show evidence of added value beyond that provided by the Framingham Risk Score or another global cardiovascular risk score plus assessment of family history, which are the only class I recommendations in the new report, meaning they should be performed in all adults.

The family history is a new class I recommendation. A positive family history under the Framingham definition is a first-generation male relative with a cardiovascular event at age 50 or younger, or by age 60 or younger in a female relative.

The new guidelines state that a global cardiovascular risk score and family history are essential for everyone, preferably starting at age 20, and should be repeated every 5 years.

For a new risk marker to be considered as useful for risk prediction, it must be shown to be a statistically independent predictor after an accounting for established risk factors. Beyond that, it must also be shown to change predictive risk sufficiently to alter recommended therapy. And then it must be shown that using the novel marker to sort patients and treat them accordingly would actually yield better clinical outcomes than if the marker had not been used, said Dr. Greenland, professor of medicine and preventive medicine at Northwestern University in Chicago.

“This is a big question for almost all of our biomarkers in cardiovascular medicine, where we can perhaps show improvement in prediction, but it's not quite so clear we can show improvement in clinical outcomes,” he said. “Generally speaking, we haven't seen much evidence of improvement of risk prediction with the new markers when you look at the whole picture. The one exception, I would say, is measurement of coronary artery calcium. I came to this as a major skeptic about coronary calcium, and only after seeing some data did I come to believe that coronary calcium might actually have clinical impact. But even with coronary calcium, I think we're too early in the evaluation process to recommend routine use beyond standard risk measurement.”

Indeed, coronary artery calcium scoring gets a class IIa recommendation (meaning it's reasonable for cardiovascular risk assessment) only in asymptomatic adults who are at intermediate risk, as defined by their global Framingham-type risk assessment, with an estimated 10%-20% risk of a cardiovascular event in the next 10 years. Coronary calcium scoring gets a lesser IIb rating (meaning it 'may be considered appropriate') in patients who are at low to intermediate risk, as defined by an estimated 6%-10% risk of an event over 10 years. In patients with less than a 6% 10-year risk, it gets a class III rating.

Investigators in MESA (Multi-Ethnic Study of Atherosclerosis) found that adding coronary artery calcium scores to standard cardiovascular risk factors improved risk discrimination from 77% to 82%, which the committee deemed clinically meaningful, Dr. Smith noted.

Measurement of C-reactive protein, another hot topic, is rated class III (no benefit) in asymptomatic adults who are defined as high-risk by the Adult Treatment Panel III standard of a greater than 20% 10-year risk. Similarly, CRP is class III in low-risk men younger than age 50 and in low-risk women younger than age 60.

However, CRP gets a class IIa recommendation as a guide to deciding on statin therapy in men aged 50 or older and in women aged 60 and older with an LDL cholesterol level of less than 130 mg/dL. It gets a class IIb recommendation in asymptomatic men and women aged 50 and 60 years, respectively, or younger.

The full 54-page guideline was released online in Circulation during the conference, and it is available at http://circ.ahajournals.org/cgi/reprint/CIR.0b013e3182051b4cv1

Dr. Smith declared having no relevant financial interests. Dr. Greenland disclosed serving as a consultant to Pfizer, General Electric, and Toshiba.

'Genetic testing is a sexy area right now, but we didn't see it as being ready or as having shown added value.'

Source DR. SMITH

CHICAGO – New American College of Cardiology/American Heart Association guidelines on cardiovascular risk assessment in asymptomatic adults may be better remembered for the tests and procedures that received a thumbs-down rather than for those endorsed for routine use.

For example, genetic testing was among the newer, often glamorous tests that have captured intense public and physician interest, yet they were classified as class III – meaning they're deemed not useful and may be harmful. In other words, don't do them in people without symptoms of heart disease.

“Genetic testing is a sexy area right now, but we didn't see it as being ready or as having shown added value,” Dr. Sidney C. Smith Jr. said in a press briefing on the new guidelines held during the meeting.

Other tests that were rated class III included advanced lipid testing with measurement of apolipoproteins and particle size and density, MRI for the detection of arterial plaque, measurement of natriuretic peptide levels, and coronary CT angiography.

“You'll hear a lot of discussion about the value of coronary CT angiography in people who come into the emergency department with chest pain, but that's a very different population,” said Dr. Smith, a member of the risk assessment guideline writing committee and immediate past chair of the ACC/AHA task force on practice guidelines.

Stress echocardiography, measures of arterial stiffness, and assessment of flow-mediated dilation also received class III status, noted Dr. Smith, professor of medicine and director of the center for cardiovascular science and medicine at the University of North Carolina, Chapel Hill.

In his Ancel Keys Memorial Lecture delivered at the AHA conference, Dr. Philip Greenland, chair of the guideline writing committee, explained that new diagnostic tests have to clear a high bar: They must show evidence of added value beyond that provided by the Framingham Risk Score or another global cardiovascular risk score plus assessment of family history, which are the only class I recommendations in the new report, meaning they should be performed in all adults.

The family history is a new class I recommendation. A positive family history under the Framingham definition is a first-generation male relative with a cardiovascular event at age 50 or younger, or by age 60 or younger in a female relative.

The new guidelines state that a global cardiovascular risk score and family history are essential for everyone, preferably starting at age 20, and should be repeated every 5 years.

For a new risk marker to be considered as useful for risk prediction, it must be shown to be a statistically independent predictor after an accounting for established risk factors. Beyond that, it must also be shown to change predictive risk sufficiently to alter recommended therapy. And then it must be shown that using the novel marker to sort patients and treat them accordingly would actually yield better clinical outcomes than if the marker had not been used, said Dr. Greenland, professor of medicine and preventive medicine at Northwestern University in Chicago.

“This is a big question for almost all of our biomarkers in cardiovascular medicine, where we can perhaps show improvement in prediction, but it's not quite so clear we can show improvement in clinical outcomes,” he said. “Generally speaking, we haven't seen much evidence of improvement of risk prediction with the new markers when you look at the whole picture. The one exception, I would say, is measurement of coronary artery calcium. I came to this as a major skeptic about coronary calcium, and only after seeing some data did I come to believe that coronary calcium might actually have clinical impact. But even with coronary calcium, I think we're too early in the evaluation process to recommend routine use beyond standard risk measurement.”

Indeed, coronary artery calcium scoring gets a class IIa recommendation (meaning it's reasonable for cardiovascular risk assessment) only in asymptomatic adults who are at intermediate risk, as defined by their global Framingham-type risk assessment, with an estimated 10%-20% risk of a cardiovascular event in the next 10 years. Coronary calcium scoring gets a lesser IIb rating (meaning it 'may be considered appropriate') in patients who are at low to intermediate risk, as defined by an estimated 6%-10% risk of an event over 10 years. In patients with less than a 6% 10-year risk, it gets a class III rating.

Investigators in MESA (Multi-Ethnic Study of Atherosclerosis) found that adding coronary artery calcium scores to standard cardiovascular risk factors improved risk discrimination from 77% to 82%, which the committee deemed clinically meaningful, Dr. Smith noted.

Measurement of C-reactive protein, another hot topic, is rated class III (no benefit) in asymptomatic adults who are defined as high-risk by the Adult Treatment Panel III standard of a greater than 20% 10-year risk. Similarly, CRP is class III in low-risk men younger than age 50 and in low-risk women younger than age 60.

However, CRP gets a class IIa recommendation as a guide to deciding on statin therapy in men aged 50 or older and in women aged 60 and older with an LDL cholesterol level of less than 130 mg/dL. It gets a class IIb recommendation in asymptomatic men and women aged 50 and 60 years, respectively, or younger.

The full 54-page guideline was released online in Circulation during the conference, and it is available at http://circ.ahajournals.org/cgi/reprint/CIR.0b013e3182051b4cv1

Dr. Smith declared having no relevant financial interests. Dr. Greenland disclosed serving as a consultant to Pfizer, General Electric, and Toshiba.

'Genetic testing is a sexy area right now, but we didn't see it as being ready or as having shown added value.'

Source DR. SMITH

 DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an NSAID or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid didn't differ significantly from that in patients on an NSAID. Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID.

In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller of the Harvard Injury Control Research Center, Boston.

“Our findings … suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed. These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months. Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Asked why he thought short-acting opioids were prescribed 13 times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

Long-acting opioids provide adequate relief in a time scale that's similar to that for short-acting drugs.

Source DR. MILLER

 DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an NSAID or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid didn't differ significantly from that in patients on an NSAID. Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID.

In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller of the Harvard Injury Control Research Center, Boston.

“Our findings … suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed. These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months. Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Asked why he thought short-acting opioids were prescribed 13 times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

Long-acting opioids provide adequate relief in a time scale that's similar to that for short-acting drugs.

Source DR. MILLER

 DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an NSAID or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid didn't differ significantly from that in patients on an NSAID. Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID.

In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller of the Harvard Injury Control Research Center, Boston.

“Our findings … suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed. These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months. Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Asked why he thought short-acting opioids were prescribed 13 times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

Long-acting opioids provide adequate relief in a time scale that's similar to that for short-acting drugs.

Source DR. MILLER

DENVER – Even before the U.S. Preventive Services Task Force issued its controversial 2009 recommendation, only a slim majority of women with health insurance were getting even one mammogram every 2 years.

Thus, the utilization rate for mammography – be it standard, digital, or MRI – remains well below recommendations, Judie Mopsik said at the San Antonio Breast Cancer Symposium.

She presented an analysis of longitudinal medical claims data for 4.5 million women aged 18 years or older covered by a national health insurance company with 20 million enrollees.

These were women with full access to preventive care. During the study period, 2006-2008, 1.9 million of the 4.5 million women had a mammogram.

The mammographic screening rate during this 2-year window was 9% among 18- to 39-year-olds.

The rate was 53% among women aged 40-49 years, a group for whom routine screening isn't recommended in the latest USPSTF guidelines.

At the time of the study, however, the USPSTF's previous guidelines were in effect, and those guidelines recommended mammography every 1-2 years starting at age 40, noted Ms. Mopsik, who is president of the Council of Professional Associations on Federal Statistics and vice president for business development at the Lewin Group in Falls Church, Va.

The screening rate within the 2-year study window was 59% among women in their 50s, for whom mammography is routinely recommended at least once every 2 years.

And the screening rate was 49% in women aged 60 years or older.

Among women who had two or more mammograms during the 2-year study period, the majority – 56%-84% depending upon the age group – had their most recent mammogram within 11-18 months of their prior mammogram.

This is the population of assiduous adherents to preventive medicine likely to find particularly troubling the USPSTF's reversal of its longtime guidelines calling for screening every 1-2 years, particularly since the American Cancer Society still recommends annual mammography starting at age 40 years.

The study was supported by the National Center for Health Statistics. Ms. Mopsik declared having no relevant financial interests.

DENVER – Even before the U.S. Preventive Services Task Force issued its controversial 2009 recommendation, only a slim majority of women with health insurance were getting even one mammogram every 2 years.

Thus, the utilization rate for mammography – be it standard, digital, or MRI – remains well below recommendations, Judie Mopsik said at the San Antonio Breast Cancer Symposium.

She presented an analysis of longitudinal medical claims data for 4.5 million women aged 18 years or older covered by a national health insurance company with 20 million enrollees.

These were women with full access to preventive care. During the study period, 2006-2008, 1.9 million of the 4.5 million women had a mammogram.

The mammographic screening rate during this 2-year window was 9% among 18- to 39-year-olds.

The rate was 53% among women aged 40-49 years, a group for whom routine screening isn't recommended in the latest USPSTF guidelines.

At the time of the study, however, the USPSTF's previous guidelines were in effect, and those guidelines recommended mammography every 1-2 years starting at age 40, noted Ms. Mopsik, who is president of the Council of Professional Associations on Federal Statistics and vice president for business development at the Lewin Group in Falls Church, Va.

The screening rate within the 2-year study window was 59% among women in their 50s, for whom mammography is routinely recommended at least once every 2 years.

And the screening rate was 49% in women aged 60 years or older.

Among women who had two or more mammograms during the 2-year study period, the majority – 56%-84% depending upon the age group – had their most recent mammogram within 11-18 months of their prior mammogram.

This is the population of assiduous adherents to preventive medicine likely to find particularly troubling the USPSTF's reversal of its longtime guidelines calling for screening every 1-2 years, particularly since the American Cancer Society still recommends annual mammography starting at age 40 years.

The study was supported by the National Center for Health Statistics. Ms. Mopsik declared having no relevant financial interests.

DENVER – Even before the U.S. Preventive Services Task Force issued its controversial 2009 recommendation, only a slim majority of women with health insurance were getting even one mammogram every 2 years.

Thus, the utilization rate for mammography – be it standard, digital, or MRI – remains well below recommendations, Judie Mopsik said at the San Antonio Breast Cancer Symposium.

She presented an analysis of longitudinal medical claims data for 4.5 million women aged 18 years or older covered by a national health insurance company with 20 million enrollees.

These were women with full access to preventive care. During the study period, 2006-2008, 1.9 million of the 4.5 million women had a mammogram.

The mammographic screening rate during this 2-year window was 9% among 18- to 39-year-olds.

The rate was 53% among women aged 40-49 years, a group for whom routine screening isn't recommended in the latest USPSTF guidelines.

At the time of the study, however, the USPSTF's previous guidelines were in effect, and those guidelines recommended mammography every 1-2 years starting at age 40, noted Ms. Mopsik, who is president of the Council of Professional Associations on Federal Statistics and vice president for business development at the Lewin Group in Falls Church, Va.

The screening rate within the 2-year study window was 59% among women in their 50s, for whom mammography is routinely recommended at least once every 2 years.

And the screening rate was 49% in women aged 60 years or older.

Among women who had two or more mammograms during the 2-year study period, the majority – 56%-84% depending upon the age group – had their most recent mammogram within 11-18 months of their prior mammogram.

This is the population of assiduous adherents to preventive medicine likely to find particularly troubling the USPSTF's reversal of its longtime guidelines calling for screening every 1-2 years, particularly since the American Cancer Society still recommends annual mammography starting at age 40 years.

The study was supported by the National Center for Health Statistics. Ms. Mopsik declared having no relevant financial interests.

Major Finding: At weeks 8 and 12, the combination therapy group had 73% and 74% reductions from baseline in Propionibacterium acnes, compared with reductions of 16% and 14% in controls.

Data Source: A large, double-blind multicenter trial involving 459 patients with severe acne who were randomized to once-daily application of Epiduo in the evening plus 100 mg/day of doxycycline hyclate for 12 weeks, or to vehicle plus doxycycline.

Disclosures: Dr. Cruz said he had received a research grant from Galderma Laboratories, which funded the clinical trial.

GOTHENBURG, SWEDEN – Multimodal therapy with adapalene 0.1% and benzoyl peroxide 2.5% in a fixed-dose combination gel plus oral doxycycline proved safe, effective, and well tolerated for severe acne vulgaris in a large, double-blind, multicenter randomized trial.

Indeed, the combination therapy's favorable safety profile makes it a compelling first-line treatment for all but the most severe, recalcitrant cases of nodular acne, where oral isotretinoin, despite its problematic safety profile, remains the treatment of choice because of its unequalled efficacy, Dr. Alma Cruz said at the meeting.

The mechanism of benefit for adapalene 0.1%–benzoyl peroxide 2.5% fixed-dose combination gel (Epiduo) plus oral doxycycline in patients with severe acne appears to involve, at least in part, the combination therapy's ability to achieve a rapid and sustained reduction in Propionibacterium acnes as documented in the trial by serial fluorescent photography, according to Dr. Cruz, a dermatologist in Carolina, P.R.

At week 4 in the 12-week trial, patients in the combination therapy arm had a mean 60% reduction from baseline in P. acnes compared with a 22% decrease in the vehicle plus doxycycline group.

At weeks 8 and 12, the combination therapy group had 73% and 74% reductions from baseline in P. acnes, compared with reductions of 16% and 14% in controls.

The reduction in P. acnes correlated with clinical efficacy. At week 2, one-third of the ultimate reduction in total lesion count in the combination treatment arm had already been achieved, with a mean 21% reduction from baseline, compared with a 13% decrease in controls.

At week 12, patients on Epiduo plus doxycycline had a mean 64% decrease from baseline in total acne lesions, compared with a 41% reduction in controls. The combined therapy outperformed doxycycline plus vehicle in treating both inflammatory and noninflammatory lesions.

The treatment success rate as defined by a rating of clear or almost clear on the investigator's global assessment scale was 9.9% and 31.5% at weeks 8 and 12 in the combined therapy group, versus 2.6% and 8.4% in the controls.

The trial involved 459 patients with severe acne who were randomized to once-daily application of Epiduo in the evening plus 100 mg/day of doxycycline hyclate for 12 weeks, or to vehicle plus doxycycline.

The overall safety and tolerability of the combination therapy was similar to that of the vehicle plus doxycycline. Just under 10% of patients in both study arms reported gastrointestinal complaints believed to be due to the doxycycline.

A week-12 patient satisfaction survey showed 76% of patients in the combined therapy arm were satisfied or very satisfied overall with their treatment, compared with 50% of the controls. Sixty-seven percent of patients in the combination therapy group indicated they felt a lot better or much better about themselves since starting their therapy, as did 48% of the controls.

Major Finding: At weeks 8 and 12, the combination therapy group had 73% and 74% reductions from baseline in Propionibacterium acnes, compared with reductions of 16% and 14% in controls.

Data Source: A large, double-blind multicenter trial involving 459 patients with severe acne who were randomized to once-daily application of Epiduo in the evening plus 100 mg/day of doxycycline hyclate for 12 weeks, or to vehicle plus doxycycline.

Disclosures: Dr. Cruz said he had received a research grant from Galderma Laboratories, which funded the clinical trial.

GOTHENBURG, SWEDEN – Multimodal therapy with adapalene 0.1% and benzoyl peroxide 2.5% in a fixed-dose combination gel plus oral doxycycline proved safe, effective, and well tolerated for severe acne vulgaris in a large, double-blind, multicenter randomized trial.

Indeed, the combination therapy's favorable safety profile makes it a compelling first-line treatment for all but the most severe, recalcitrant cases of nodular acne, where oral isotretinoin, despite its problematic safety profile, remains the treatment of choice because of its unequalled efficacy, Dr. Alma Cruz said at the meeting.

The mechanism of benefit for adapalene 0.1%–benzoyl peroxide 2.5% fixed-dose combination gel (Epiduo) plus oral doxycycline in patients with severe acne appears to involve, at least in part, the combination therapy's ability to achieve a rapid and sustained reduction in Propionibacterium acnes as documented in the trial by serial fluorescent photography, according to Dr. Cruz, a dermatologist in Carolina, P.R.

At week 4 in the 12-week trial, patients in the combination therapy arm had a mean 60% reduction from baseline in P. acnes compared with a 22% decrease in the vehicle plus doxycycline group.

At weeks 8 and 12, the combination therapy group had 73% and 74% reductions from baseline in P. acnes, compared with reductions of 16% and 14% in controls.

The reduction in P. acnes correlated with clinical efficacy. At week 2, one-third of the ultimate reduction in total lesion count in the combination treatment arm had already been achieved, with a mean 21% reduction from baseline, compared with a 13% decrease in controls.

At week 12, patients on Epiduo plus doxycycline had a mean 64% decrease from baseline in total acne lesions, compared with a 41% reduction in controls. The combined therapy outperformed doxycycline plus vehicle in treating both inflammatory and noninflammatory lesions.

The treatment success rate as defined by a rating of clear or almost clear on the investigator's global assessment scale was 9.9% and 31.5% at weeks 8 and 12 in the combined therapy group, versus 2.6% and 8.4% in the controls.

The trial involved 459 patients with severe acne who were randomized to once-daily application of Epiduo in the evening plus 100 mg/day of doxycycline hyclate for 12 weeks, or to vehicle plus doxycycline.

The overall safety and tolerability of the combination therapy was similar to that of the vehicle plus doxycycline. Just under 10% of patients in both study arms reported gastrointestinal complaints believed to be due to the doxycycline.

A week-12 patient satisfaction survey showed 76% of patients in the combined therapy arm were satisfied or very satisfied overall with their treatment, compared with 50% of the controls. Sixty-seven percent of patients in the combination therapy group indicated they felt a lot better or much better about themselves since starting their therapy, as did 48% of the controls.

Major Finding: At weeks 8 and 12, the combination therapy group had 73% and 74% reductions from baseline in Propionibacterium acnes, compared with reductions of 16% and 14% in controls.

Data Source: A large, double-blind multicenter trial involving 459 patients with severe acne who were randomized to once-daily application of Epiduo in the evening plus 100 mg/day of doxycycline hyclate for 12 weeks, or to vehicle plus doxycycline.

Disclosures: Dr. Cruz said he had received a research grant from Galderma Laboratories, which funded the clinical trial.

GOTHENBURG, SWEDEN – Multimodal therapy with adapalene 0.1% and benzoyl peroxide 2.5% in a fixed-dose combination gel plus oral doxycycline proved safe, effective, and well tolerated for severe acne vulgaris in a large, double-blind, multicenter randomized trial.

Indeed, the combination therapy's favorable safety profile makes it a compelling first-line treatment for all but the most severe, recalcitrant cases of nodular acne, where oral isotretinoin, despite its problematic safety profile, remains the treatment of choice because of its unequalled efficacy, Dr. Alma Cruz said at the meeting.

The mechanism of benefit for adapalene 0.1%–benzoyl peroxide 2.5% fixed-dose combination gel (Epiduo) plus oral doxycycline in patients with severe acne appears to involve, at least in part, the combination therapy's ability to achieve a rapid and sustained reduction in Propionibacterium acnes as documented in the trial by serial fluorescent photography, according to Dr. Cruz, a dermatologist in Carolina, P.R.

At week 4 in the 12-week trial, patients in the combination therapy arm had a mean 60% reduction from baseline in P. acnes compared with a 22% decrease in the vehicle plus doxycycline group.

At weeks 8 and 12, the combination therapy group had 73% and 74% reductions from baseline in P. acnes, compared with reductions of 16% and 14% in controls.

The reduction in P. acnes correlated with clinical efficacy. At week 2, one-third of the ultimate reduction in total lesion count in the combination treatment arm had already been achieved, with a mean 21% reduction from baseline, compared with a 13% decrease in controls.

At week 12, patients on Epiduo plus doxycycline had a mean 64% decrease from baseline in total acne lesions, compared with a 41% reduction in controls. The combined therapy outperformed doxycycline plus vehicle in treating both inflammatory and noninflammatory lesions.

The treatment success rate as defined by a rating of clear or almost clear on the investigator's global assessment scale was 9.9% and 31.5% at weeks 8 and 12 in the combined therapy group, versus 2.6% and 8.4% in the controls.

The trial involved 459 patients with severe acne who were randomized to once-daily application of Epiduo in the evening plus 100 mg/day of doxycycline hyclate for 12 weeks, or to vehicle plus doxycycline.

The overall safety and tolerability of the combination therapy was similar to that of the vehicle plus doxycycline. Just under 10% of patients in both study arms reported gastrointestinal complaints believed to be due to the doxycycline.

A week-12 patient satisfaction survey showed 76% of patients in the combined therapy arm were satisfied or very satisfied overall with their treatment, compared with 50% of the controls. Sixty-seven percent of patients in the combination therapy group indicated they felt a lot better or much better about themselves since starting their therapy, as did 48% of the controls.

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the meeting.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England), who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is ubiquitous,” he said. “But there's been a gross oversight in these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the U.K.'s National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health. T

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes which concluded that most people have adequate but suboptimal levels during the summer, with a mean of 70 nmol/L. The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter moople's mean serum vitamin D falls to 48 nmol/L (BMJ 2010;340:b5664).

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year. A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the meeting.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England), who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is ubiquitous,” he said. “But there's been a gross oversight in these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the U.K.'s National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health. T

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes which concluded that most people have adequate but suboptimal levels during the summer, with a mean of 70 nmol/L. The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter moople's mean serum vitamin D falls to 48 nmol/L (BMJ 2010;340:b5664).

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year. A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the meeting.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England), who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is ubiquitous,” he said. “But there's been a gross oversight in these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the U.K.'s National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health. T

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes which concluded that most people have adequate but suboptimal levels during the summer, with a mean of 70 nmol/L. The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter moople's mean serum vitamin D falls to 48 nmol/L (BMJ 2010;340:b5664).

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year. A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

Major Finding: The age-adjusted prevalence of diabetes was 4% in nonusers and significantly lower at 3% in marijuana users. In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, marijuana users had a 66% lower likelihood of having diabetes.

Data Source: A cross-sectional study involving 10,896 NHANES III participants aged 20-59 years.

Disclosures: The study was funded by Omics Biotechnology, which is pursuing potential medical applications for nonpsychotropic cannabinoid receptor agonists. Dr. Shaheen declared she has no relevant financial relationships.

DENVER – Marijuana use may be associated with a markedly decreased risk of diabetes.

A provocative new analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III) indicates marijuana users had 66% lower odds of having diabetes after adjustment for numerous potential confounding factors, Dr. Magda Shaheen reported at the meeting.

This robust observed benefit has a biologically plausible mechanism, noted Dr. Shaheen.

In addition to defects in pancreatic beta-cell function and insulin sensitivity, the pathogenesis of diabetes is thought to involve systemic inflammation. Marijuana contains bioactive cannabinoids that have been shown to have an anti-inflammatory effect. This was borne out in the NHANES III analysis, where the prevalence of an elevated C-reactive protein level in excess of 0.5 mg/dL was significantly higher in nonusers of marijuana, at 18.9%, than in past users, with a 13% prevalence of elevated CRP, current light users (16%), or current heavy users of the illicit drug (9%), according to Dr. Shaheen of Charles R. Drew University of Medicine and Science, Los Angeles.

The study population consisted of 10,896 NHANES III participants aged 20-59 years; they constituted a statistically representative sample of the broader U.S. civilian population in 1988-94, when the survey was conducted.

The majority of subjects – 55% – reported never having used marijuana. Another 37% were past users, meaning they hadn't used marijuana during the previous month. The 6% of subjects who reported currently using the drug 1-4 days per month were categorized as current light users, while 3.3% of subjects were current heavier users.

The age-adjusted prevalence of diabetes in this cross-sectional study was 4% in nonusers and significantly lower at 3% in marijuana users.

Current and past users of marijuana were significantly younger, had a lower body mass index, and were more physically active than were nonusers. They were also more likely to smoke cigarettes, drink alcohol, and use cocaine. In addition, they were more likely to have an HDL level greater than 40 mg/dL and had lower mean total cholesterol, LDL, and triglyceride levels.

In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, the marijuana users were found to have a 66% lower likelihood of being diabetic. This benefit was confined to the 41- to 59-year-old age group, where the reduction in diabetes risk associated with marijuana use was 67%. In contrast, the 7% reduction in risk among 20- to 40-year-olds was not statistically significant. These findings could be the result of the markedly higher occurrence of diabetes during middle age.

Unlike in diabetes, marijuana use was not associated with a lower prevalence of the other chronic diseases that Dr. Shaheen and coworkers looked at in which systemic inflammation also plays a role: myocardial infarction, heart failure, stroke, and hypertension.

“This was probably due to the lower prevalence of these diseases in this age group,” she commented.

Dr. Shaheen noted that the lowest prevalence of diabetes was found in current light users of marijuana, although past users and current heavy users also had lower rates than did nonusers.

“This finding in light marijuana users is similar to the effect of alcohol on diabetes mellitus and the metabolic syndrome. Studies have shown that mild alcohol use was associated with a lower prevalence of diabetes and metabolic syndrome, and higher use was associated with a higher prevalence,” she observed.

Dr. Shaheen stressed that as this was a cross-sectional study, it can't establish causality. The findings, while provocative, ought to be interpreted cautiously.

“Prospective studies need to be performed in rodents and humans to determine a causal relationship between cannabinoid receptor activation and diabetes.

Until those studies are performed, we do not advocate the use of marijuana in patients at risk for diabetes mellitus,” the investigator stressed.

Marijuana use was not associated with a lower rate of MI, heart failure, stroke, and hypertension.

Source DR. SHAHEEN

Major Finding: The age-adjusted prevalence of diabetes was 4% in nonusers and significantly lower at 3% in marijuana users. In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, marijuana users had a 66% lower likelihood of having diabetes.

Data Source: A cross-sectional study involving 10,896 NHANES III participants aged 20-59 years.

Disclosures: The study was funded by Omics Biotechnology, which is pursuing potential medical applications for nonpsychotropic cannabinoid receptor agonists. Dr. Shaheen declared she has no relevant financial relationships.

DENVER – Marijuana use may be associated with a markedly decreased risk of diabetes.

A provocative new analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III) indicates marijuana users had 66% lower odds of having diabetes after adjustment for numerous potential confounding factors, Dr. Magda Shaheen reported at the meeting.

This robust observed benefit has a biologically plausible mechanism, noted Dr. Shaheen.

In addition to defects in pancreatic beta-cell function and insulin sensitivity, the pathogenesis of diabetes is thought to involve systemic inflammation. Marijuana contains bioactive cannabinoids that have been shown to have an anti-inflammatory effect. This was borne out in the NHANES III analysis, where the prevalence of an elevated C-reactive protein level in excess of 0.5 mg/dL was significantly higher in nonusers of marijuana, at 18.9%, than in past users, with a 13% prevalence of elevated CRP, current light users (16%), or current heavy users of the illicit drug (9%), according to Dr. Shaheen of Charles R. Drew University of Medicine and Science, Los Angeles.

The study population consisted of 10,896 NHANES III participants aged 20-59 years; they constituted a statistically representative sample of the broader U.S. civilian population in 1988-94, when the survey was conducted.

The majority of subjects – 55% – reported never having used marijuana. Another 37% were past users, meaning they hadn't used marijuana during the previous month. The 6% of subjects who reported currently using the drug 1-4 days per month were categorized as current light users, while 3.3% of subjects were current heavier users.

The age-adjusted prevalence of diabetes in this cross-sectional study was 4% in nonusers and significantly lower at 3% in marijuana users.

Current and past users of marijuana were significantly younger, had a lower body mass index, and were more physically active than were nonusers. They were also more likely to smoke cigarettes, drink alcohol, and use cocaine. In addition, they were more likely to have an HDL level greater than 40 mg/dL and had lower mean total cholesterol, LDL, and triglyceride levels.

In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, the marijuana users were found to have a 66% lower likelihood of being diabetic. This benefit was confined to the 41- to 59-year-old age group, where the reduction in diabetes risk associated with marijuana use was 67%. In contrast, the 7% reduction in risk among 20- to 40-year-olds was not statistically significant. These findings could be the result of the markedly higher occurrence of diabetes during middle age.

Unlike in diabetes, marijuana use was not associated with a lower prevalence of the other chronic diseases that Dr. Shaheen and coworkers looked at in which systemic inflammation also plays a role: myocardial infarction, heart failure, stroke, and hypertension.

“This was probably due to the lower prevalence of these diseases in this age group,” she commented.

Dr. Shaheen noted that the lowest prevalence of diabetes was found in current light users of marijuana, although past users and current heavy users also had lower rates than did nonusers.

“This finding in light marijuana users is similar to the effect of alcohol on diabetes mellitus and the metabolic syndrome. Studies have shown that mild alcohol use was associated with a lower prevalence of diabetes and metabolic syndrome, and higher use was associated with a higher prevalence,” she observed.

Dr. Shaheen stressed that as this was a cross-sectional study, it can't establish causality. The findings, while provocative, ought to be interpreted cautiously.

“Prospective studies need to be performed in rodents and humans to determine a causal relationship between cannabinoid receptor activation and diabetes.

Until those studies are performed, we do not advocate the use of marijuana in patients at risk for diabetes mellitus,” the investigator stressed.

Marijuana use was not associated with a lower rate of MI, heart failure, stroke, and hypertension.

Source DR. SHAHEEN

Major Finding: The age-adjusted prevalence of diabetes was 4% in nonusers and significantly lower at 3% in marijuana users. In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, marijuana users had a 66% lower likelihood of having diabetes.

Data Source: A cross-sectional study involving 10,896 NHANES III participants aged 20-59 years.

Disclosures: The study was funded by Omics Biotechnology, which is pursuing potential medical applications for nonpsychotropic cannabinoid receptor agonists. Dr. Shaheen declared she has no relevant financial relationships.

DENVER – Marijuana use may be associated with a markedly decreased risk of diabetes.

A provocative new analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III) indicates marijuana users had 66% lower odds of having diabetes after adjustment for numerous potential confounding factors, Dr. Magda Shaheen reported at the meeting.

This robust observed benefit has a biologically plausible mechanism, noted Dr. Shaheen.

In addition to defects in pancreatic beta-cell function and insulin sensitivity, the pathogenesis of diabetes is thought to involve systemic inflammation. Marijuana contains bioactive cannabinoids that have been shown to have an anti-inflammatory effect. This was borne out in the NHANES III analysis, where the prevalence of an elevated C-reactive protein level in excess of 0.5 mg/dL was significantly higher in nonusers of marijuana, at 18.9%, than in past users, with a 13% prevalence of elevated CRP, current light users (16%), or current heavy users of the illicit drug (9%), according to Dr. Shaheen of Charles R. Drew University of Medicine and Science, Los Angeles.

The study population consisted of 10,896 NHANES III participants aged 20-59 years; they constituted a statistically representative sample of the broader U.S. civilian population in 1988-94, when the survey was conducted.

The majority of subjects – 55% – reported never having used marijuana. Another 37% were past users, meaning they hadn't used marijuana during the previous month. The 6% of subjects who reported currently using the drug 1-4 days per month were categorized as current light users, while 3.3% of subjects were current heavier users.

The age-adjusted prevalence of diabetes in this cross-sectional study was 4% in nonusers and significantly lower at 3% in marijuana users.

Current and past users of marijuana were significantly younger, had a lower body mass index, and were more physically active than were nonusers. They were also more likely to smoke cigarettes, drink alcohol, and use cocaine. In addition, they were more likely to have an HDL level greater than 40 mg/dL and had lower mean total cholesterol, LDL, and triglyceride levels.

In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, the marijuana users were found to have a 66% lower likelihood of being diabetic. This benefit was confined to the 41- to 59-year-old age group, where the reduction in diabetes risk associated with marijuana use was 67%. In contrast, the 7% reduction in risk among 20- to 40-year-olds was not statistically significant. These findings could be the result of the markedly higher occurrence of diabetes during middle age.

Unlike in diabetes, marijuana use was not associated with a lower prevalence of the other chronic diseases that Dr. Shaheen and coworkers looked at in which systemic inflammation also plays a role: myocardial infarction, heart failure, stroke, and hypertension.

“This was probably due to the lower prevalence of these diseases in this age group,” she commented.

Dr. Shaheen noted that the lowest prevalence of diabetes was found in current light users of marijuana, although past users and current heavy users also had lower rates than did nonusers.

“This finding in light marijuana users is similar to the effect of alcohol on diabetes mellitus and the metabolic syndrome. Studies have shown that mild alcohol use was associated with a lower prevalence of diabetes and metabolic syndrome, and higher use was associated with a higher prevalence,” she observed.

Dr. Shaheen stressed that as this was a cross-sectional study, it can't establish causality. The findings, while provocative, ought to be interpreted cautiously.

“Prospective studies need to be performed in rodents and humans to determine a causal relationship between cannabinoid receptor activation and diabetes.

Until those studies are performed, we do not advocate the use of marijuana in patients at risk for diabetes mellitus,” the investigator stressed.

Marijuana use was not associated with a lower rate of MI, heart failure, stroke, and hypertension.

Source DR. SHAHEEN