Jennie Smith

Nearly 1.3 million Europeans will die from cancer this year, according to epidemiologists who predict that age-standardized death rates for most cancers will have dropped or remained flat since 2007 with the exception of lung cancer in women.

Based on a close analysis of continuing trends in the European Union, an estimated 1,281,436 E.U. residents – 721,252 men and 560,184 women of all ages – will die of cancer in 2011, they said. Overall, E.U. cancer deaths have will have dropped 7% in men and 6% in women over 5 years, from 153.8 per 100,000 to 142.8 per 100,000 in men, and from 90.7 to 85.3 in women, they say – a continuation of longer-term patterns of decline.

For their research, published Feb. 9 in Annals of Oncology (Annals Oncol. 2011 Feb. 9 [doi:10.1093/annonc/mdq774]), epidemiologist Dr. Carlo La Vecchia of the University of Milan, along with Dr. Fabio Levi of Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland, and colleagues, examined World Health Organization mortality records to identify deaths from stomach, colorectal, pancreatic, lung, breast, uterine, cervical, and prostate cancers, along with leukemia deaths and total cancer deaths, for all EU countries besides Cyprus between 1970 and 2007.

They also used the most recent national cancer-death data available (the oldest from 2005 and the newest from 2008) for France, Germany, Italy, Poland, Spain, and the United Kingdom, Europe’s six most populous countries.

Dr. La Vecchia, Dr. Levi, and colleagues identified a downward trend in mortality for all cancers studied, except for pancreatic cancer, which was predicted to remain flat for men and increase very slightly among women in 2011, they said. They also noted that the one former Eastern bloc country, Poland, among the six populous countries studied, had higher overall death rates and less impressive declines than did the others. For example, estimated mortality rates for uterine cancer in Poland were three times higher than those projected for Germany: 7.9 and 2.6 per 100,000 women, respectively.

The European patterns reported stand in contrast to new global trends published in a Feb 4 report by the American Cancer Society (Global Cancer Facts & Figures 2nd Edition), which highlights an increasing portion of cancer deaths in developing countries attributable to lifestyle changes such as smoking, unhealthy diet, and physical inactivity as opposed to infections such as hepatitis B virus (HBV), human immunodeficiency virus, human papillomavirus, and helicobacter pylori. For example, male lung cancer mortality, which is declining in Europe, has been increasing in China and other countries in Asia and Africa. And breast cancer (likely reflective of changes in reproductive patterns, obesity, physical inactivity, and delayed breast cancer screening) now leads in cancer deaths among women in developing countries, as opposed to cervical cancer, according to the ACS report.

Yet even within Europe, divides persist along national and economic lines. In a report presented to the European Parliament Feb. 9 by the European Society for Pediatric Oncology, investigators found that Eastern European countries with a heavy oncology burden tended not to collaborate in research with countries with better-developed research structures, and that pediatric cancer patients suffered as a result.

Dr. La Vecchia said in an interview that Poland’s high mortality, related to drug access and quality of treatment, was representative of other former Eastern bloc countries in the European Union. "It’s a complex problem of medical culture and organization," he said. "All central and eastern Europe countries have this problem, but there is room of improvement even in the wealthier countries."

Female lung cancer was one area that needed desperate attention throughout the European Union, Dr. La Vecchia said. While deaths from breast cancer in women are likely to continue to fall, the trend in female lung cancer deaths is rising everywhere but the United Kingdom, which at 20.33 per 100,000 women still has the highest female lung cancer mortality in the European Union, followed by Poland at 16.6 per 100,000. In both countries, more women will die from lung cancer than from breast cancer in 2011, the investigators predicted.

Overall, lung cancer deaths among E.U. women will increase from 12.55 per 100,000 in 2007 to 13.12 in 2011, the investigators predicted, while rates among men have fallen. "This suggests that the lung cancer epidemic in European women is still expanding, and the rate may ultimately approach 14 to 15 per 100,000 in 2015," the investigators wrote.

"This is essentially attributable to smoking," Dr. La Vecchia said. Bans on indoor smoking are now widespread in Western Europe, but "these have only been adopted over the last 5 years, so while you see some impact on cardiovascular disease, you don’t see any important change in cancer yet in the short term." Women, he said, are simply not quitting fast enough: "We need to concentrate on convincing women to stop smoking."

The investigators noted in their analysis that among the study’s weaknesses was the fact that its predictions were short term and could be affected by unexpected events. Also, they wrote, "These predictions are based on the most recent trends in available data." However, "if a change, or even a reversal of trends, has taken place in the last 2 or 3 years," they cautioned, the regression model would not have picked it up.

The study by Dr. La Vecchia, Dr. Levi, and colleagues was funded by the Swiss Cancer League and the Italian Association for Cancer Research. The authors reported having no conflicts of interest.

Nearly 1.3 million Europeans will die from cancer this year, according to epidemiologists who predict that age-standardized death rates for most cancers will have dropped or remained flat since 2007 with the exception of lung cancer in women.

Based on a close analysis of continuing trends in the European Union, an estimated 1,281,436 E.U. residents – 721,252 men and 560,184 women of all ages – will die of cancer in 2011, they said. Overall, E.U. cancer deaths have will have dropped 7% in men and 6% in women over 5 years, from 153.8 per 100,000 to 142.8 per 100,000 in men, and from 90.7 to 85.3 in women, they say – a continuation of longer-term patterns of decline.

For their research, published Feb. 9 in Annals of Oncology (Annals Oncol. 2011 Feb. 9 [doi:10.1093/annonc/mdq774]), epidemiologist Dr. Carlo La Vecchia of the University of Milan, along with Dr. Fabio Levi of Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland, and colleagues, examined World Health Organization mortality records to identify deaths from stomach, colorectal, pancreatic, lung, breast, uterine, cervical, and prostate cancers, along with leukemia deaths and total cancer deaths, for all EU countries besides Cyprus between 1970 and 2007.

They also used the most recent national cancer-death data available (the oldest from 2005 and the newest from 2008) for France, Germany, Italy, Poland, Spain, and the United Kingdom, Europe’s six most populous countries.

Dr. La Vecchia, Dr. Levi, and colleagues identified a downward trend in mortality for all cancers studied, except for pancreatic cancer, which was predicted to remain flat for men and increase very slightly among women in 2011, they said. They also noted that the one former Eastern bloc country, Poland, among the six populous countries studied, had higher overall death rates and less impressive declines than did the others. For example, estimated mortality rates for uterine cancer in Poland were three times higher than those projected for Germany: 7.9 and 2.6 per 100,000 women, respectively.

The European patterns reported stand in contrast to new global trends published in a Feb 4 report by the American Cancer Society (Global Cancer Facts & Figures 2nd Edition), which highlights an increasing portion of cancer deaths in developing countries attributable to lifestyle changes such as smoking, unhealthy diet, and physical inactivity as opposed to infections such as hepatitis B virus (HBV), human immunodeficiency virus, human papillomavirus, and helicobacter pylori. For example, male lung cancer mortality, which is declining in Europe, has been increasing in China and other countries in Asia and Africa. And breast cancer (likely reflective of changes in reproductive patterns, obesity, physical inactivity, and delayed breast cancer screening) now leads in cancer deaths among women in developing countries, as opposed to cervical cancer, according to the ACS report.

Yet even within Europe, divides persist along national and economic lines. In a report presented to the European Parliament Feb. 9 by the European Society for Pediatric Oncology, investigators found that Eastern European countries with a heavy oncology burden tended not to collaborate in research with countries with better-developed research structures, and that pediatric cancer patients suffered as a result.

Dr. La Vecchia said in an interview that Poland’s high mortality, related to drug access and quality of treatment, was representative of other former Eastern bloc countries in the European Union. "It’s a complex problem of medical culture and organization," he said. "All central and eastern Europe countries have this problem, but there is room of improvement even in the wealthier countries."

Female lung cancer was one area that needed desperate attention throughout the European Union, Dr. La Vecchia said. While deaths from breast cancer in women are likely to continue to fall, the trend in female lung cancer deaths is rising everywhere but the United Kingdom, which at 20.33 per 100,000 women still has the highest female lung cancer mortality in the European Union, followed by Poland at 16.6 per 100,000. In both countries, more women will die from lung cancer than from breast cancer in 2011, the investigators predicted.

Overall, lung cancer deaths among E.U. women will increase from 12.55 per 100,000 in 2007 to 13.12 in 2011, the investigators predicted, while rates among men have fallen. "This suggests that the lung cancer epidemic in European women is still expanding, and the rate may ultimately approach 14 to 15 per 100,000 in 2015," the investigators wrote.

"This is essentially attributable to smoking," Dr. La Vecchia said. Bans on indoor smoking are now widespread in Western Europe, but "these have only been adopted over the last 5 years, so while you see some impact on cardiovascular disease, you don’t see any important change in cancer yet in the short term." Women, he said, are simply not quitting fast enough: "We need to concentrate on convincing women to stop smoking."

The investigators noted in their analysis that among the study’s weaknesses was the fact that its predictions were short term and could be affected by unexpected events. Also, they wrote, "These predictions are based on the most recent trends in available data." However, "if a change, or even a reversal of trends, has taken place in the last 2 or 3 years," they cautioned, the regression model would not have picked it up.

The study by Dr. La Vecchia, Dr. Levi, and colleagues was funded by the Swiss Cancer League and the Italian Association for Cancer Research. The authors reported having no conflicts of interest.

Nearly 1.3 million Europeans will die from cancer this year, according to epidemiologists who predict that age-standardized death rates for most cancers will have dropped or remained flat since 2007 with the exception of lung cancer in women.

Based on a close analysis of continuing trends in the European Union, an estimated 1,281,436 E.U. residents – 721,252 men and 560,184 women of all ages – will die of cancer in 2011, they said. Overall, E.U. cancer deaths have will have dropped 7% in men and 6% in women over 5 years, from 153.8 per 100,000 to 142.8 per 100,000 in men, and from 90.7 to 85.3 in women, they say – a continuation of longer-term patterns of decline.

For their research, published Feb. 9 in Annals of Oncology (Annals Oncol. 2011 Feb. 9 [doi:10.1093/annonc/mdq774]), epidemiologist Dr. Carlo La Vecchia of the University of Milan, along with Dr. Fabio Levi of Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland, and colleagues, examined World Health Organization mortality records to identify deaths from stomach, colorectal, pancreatic, lung, breast, uterine, cervical, and prostate cancers, along with leukemia deaths and total cancer deaths, for all EU countries besides Cyprus between 1970 and 2007.

They also used the most recent national cancer-death data available (the oldest from 2005 and the newest from 2008) for France, Germany, Italy, Poland, Spain, and the United Kingdom, Europe’s six most populous countries.

Dr. La Vecchia, Dr. Levi, and colleagues identified a downward trend in mortality for all cancers studied, except for pancreatic cancer, which was predicted to remain flat for men and increase very slightly among women in 2011, they said. They also noted that the one former Eastern bloc country, Poland, among the six populous countries studied, had higher overall death rates and less impressive declines than did the others. For example, estimated mortality rates for uterine cancer in Poland were three times higher than those projected for Germany: 7.9 and 2.6 per 100,000 women, respectively.

The European patterns reported stand in contrast to new global trends published in a Feb 4 report by the American Cancer Society (Global Cancer Facts & Figures 2nd Edition), which highlights an increasing portion of cancer deaths in developing countries attributable to lifestyle changes such as smoking, unhealthy diet, and physical inactivity as opposed to infections such as hepatitis B virus (HBV), human immunodeficiency virus, human papillomavirus, and helicobacter pylori. For example, male lung cancer mortality, which is declining in Europe, has been increasing in China and other countries in Asia and Africa. And breast cancer (likely reflective of changes in reproductive patterns, obesity, physical inactivity, and delayed breast cancer screening) now leads in cancer deaths among women in developing countries, as opposed to cervical cancer, according to the ACS report.

Yet even within Europe, divides persist along national and economic lines. In a report presented to the European Parliament Feb. 9 by the European Society for Pediatric Oncology, investigators found that Eastern European countries with a heavy oncology burden tended not to collaborate in research with countries with better-developed research structures, and that pediatric cancer patients suffered as a result.

Dr. La Vecchia said in an interview that Poland’s high mortality, related to drug access and quality of treatment, was representative of other former Eastern bloc countries in the European Union. "It’s a complex problem of medical culture and organization," he said. "All central and eastern Europe countries have this problem, but there is room of improvement even in the wealthier countries."

Female lung cancer was one area that needed desperate attention throughout the European Union, Dr. La Vecchia said. While deaths from breast cancer in women are likely to continue to fall, the trend in female lung cancer deaths is rising everywhere but the United Kingdom, which at 20.33 per 100,000 women still has the highest female lung cancer mortality in the European Union, followed by Poland at 16.6 per 100,000. In both countries, more women will die from lung cancer than from breast cancer in 2011, the investigators predicted.

Overall, lung cancer deaths among E.U. women will increase from 12.55 per 100,000 in 2007 to 13.12 in 2011, the investigators predicted, while rates among men have fallen. "This suggests that the lung cancer epidemic in European women is still expanding, and the rate may ultimately approach 14 to 15 per 100,000 in 2015," the investigators wrote.

"This is essentially attributable to smoking," Dr. La Vecchia said. Bans on indoor smoking are now widespread in Western Europe, but "these have only been adopted over the last 5 years, so while you see some impact on cardiovascular disease, you don’t see any important change in cancer yet in the short term." Women, he said, are simply not quitting fast enough: "We need to concentrate on convincing women to stop smoking."

The investigators noted in their analysis that among the study’s weaknesses was the fact that its predictions were short term and could be affected by unexpected events. Also, they wrote, "These predictions are based on the most recent trends in available data." However, "if a change, or even a reversal of trends, has taken place in the last 2 or 3 years," they cautioned, the regression model would not have picked it up.

The study by Dr. La Vecchia, Dr. Levi, and colleagues was funded by the Swiss Cancer League and the Italian Association for Cancer Research. The authors reported having no conflicts of interest.

The Food and Drug Administration said Feb. 4 that it had approved 17-alpha-hydroxyprogesterone caproate, a progesterone injection also known as 17P, for the prevention of recurrent preterm birth in women with singleton pregnancies.

The FDA said in a press statement that it had approved 17P (Makena) under the agency’s accelerated approval regulations that allow drugs to be approved based on a surrogate end-point benefit that is "reasonably likely to predict a clinical benefit."

Hydroxyprogesterone caproate was initially approved in 1956 for treatment and prevention of recurrent miscarriage, among other indications, but was withdrawn in 2000 because of manufacturing problems. Hospital pharmacies continued to mix the compound, and it remained available in many settings.

The March of Dimes said in a statement Feb. 4 that it welcomed 17P’s approval. "Prior to today’s approval of Makena, health care providers ordered prescriptions of 17P from compounding pharmacies; however, many eligible patients faced logistical and financial barriers to access. FDA approval means the drug now will be widely available."

The drug was first marketed in the 1950s as Delalutin. It was resubmitted to the FDA in 2006 as Gestiva by a California firm, and will now be marketed by Ther-Rx Corp., K-V Pharmaceutical’s branded drug subsidiary, as Makena.*

The approval comes nearly 5 years after an FDA advisory panel voted in 17P’s favor, based on results from a publicly funded, randomized, double-blind placebo-controlled trial of 463 women with at least 1 preterm delivery (N. Engl. J. Med. 2003;348:2379-85). That trial showed that women receiving weekly injections of 250 mg of 17P, starting at 20 weeks and continuing to 36 weeks or delivery, saw a 24% reduced risk of delivery before 37 weeks compared with the control group. The study also showed reductions in the rates of preterm delivery before 35 weeks and before 32 weeks in the treatment arm.

After the FDA panel’s vote in August 2006, the agency demanded further safety studies, including now-completed studies of children born to women taking 17P, from the medicine’s then-developer, which later sold its rights to 17P. In 2010 the drug’s current developer, Hologic, resubmitted its filing for 17P.

The FDA said Feb 4 that the drug’s approval comes with the manufacturer’s responsibility to complete ongoing confirmatory studies, including a new infant follow-up study, expected to end in 2018 and to include between 580 and 750 infants.

* CORRECTION, 2/17/2011: The original version of this article incorrectly stated that Makena will be marketed by Hologic, Inc. The drug will instead be marketed by Ther-Rx Corp., K-V Pharmaceutical’s branded drug subsidiary. Rights to Makena were transferred from Hologic, Inc. to K-V after the FDA approved the drug.

The Food and Drug Administration said Feb. 4 that it had approved 17-alpha-hydroxyprogesterone caproate, a progesterone injection also known as 17P, for the prevention of recurrent preterm birth in women with singleton pregnancies.

The FDA said in a press statement that it had approved 17P (Makena) under the agency’s accelerated approval regulations that allow drugs to be approved based on a surrogate end-point benefit that is "reasonably likely to predict a clinical benefit."

Hydroxyprogesterone caproate was initially approved in 1956 for treatment and prevention of recurrent miscarriage, among other indications, but was withdrawn in 2000 because of manufacturing problems. Hospital pharmacies continued to mix the compound, and it remained available in many settings.

The March of Dimes said in a statement Feb. 4 that it welcomed 17P’s approval. "Prior to today’s approval of Makena, health care providers ordered prescriptions of 17P from compounding pharmacies; however, many eligible patients faced logistical and financial barriers to access. FDA approval means the drug now will be widely available."

The drug was first marketed in the 1950s as Delalutin. It was resubmitted to the FDA in 2006 as Gestiva by a California firm, and will now be marketed by Ther-Rx Corp., K-V Pharmaceutical’s branded drug subsidiary, as Makena.*

The approval comes nearly 5 years after an FDA advisory panel voted in 17P’s favor, based on results from a publicly funded, randomized, double-blind placebo-controlled trial of 463 women with at least 1 preterm delivery (N. Engl. J. Med. 2003;348:2379-85). That trial showed that women receiving weekly injections of 250 mg of 17P, starting at 20 weeks and continuing to 36 weeks or delivery, saw a 24% reduced risk of delivery before 37 weeks compared with the control group. The study also showed reductions in the rates of preterm delivery before 35 weeks and before 32 weeks in the treatment arm.

After the FDA panel’s vote in August 2006, the agency demanded further safety studies, including now-completed studies of children born to women taking 17P, from the medicine’s then-developer, which later sold its rights to 17P. In 2010 the drug’s current developer, Hologic, resubmitted its filing for 17P.

The FDA said Feb 4 that the drug’s approval comes with the manufacturer’s responsibility to complete ongoing confirmatory studies, including a new infant follow-up study, expected to end in 2018 and to include between 580 and 750 infants.

* CORRECTION, 2/17/2011: The original version of this article incorrectly stated that Makena will be marketed by Hologic, Inc. The drug will instead be marketed by Ther-Rx Corp., K-V Pharmaceutical’s branded drug subsidiary. Rights to Makena were transferred from Hologic, Inc. to K-V after the FDA approved the drug.

The Food and Drug Administration said Feb. 4 that it had approved 17-alpha-hydroxyprogesterone caproate, a progesterone injection also known as 17P, for the prevention of recurrent preterm birth in women with singleton pregnancies.

The FDA said in a press statement that it had approved 17P (Makena) under the agency’s accelerated approval regulations that allow drugs to be approved based on a surrogate end-point benefit that is "reasonably likely to predict a clinical benefit."

Hydroxyprogesterone caproate was initially approved in 1956 for treatment and prevention of recurrent miscarriage, among other indications, but was withdrawn in 2000 because of manufacturing problems. Hospital pharmacies continued to mix the compound, and it remained available in many settings.

The March of Dimes said in a statement Feb. 4 that it welcomed 17P’s approval. "Prior to today’s approval of Makena, health care providers ordered prescriptions of 17P from compounding pharmacies; however, many eligible patients faced logistical and financial barriers to access. FDA approval means the drug now will be widely available."

The drug was first marketed in the 1950s as Delalutin. It was resubmitted to the FDA in 2006 as Gestiva by a California firm, and will now be marketed by Ther-Rx Corp., K-V Pharmaceutical’s branded drug subsidiary, as Makena.*

The approval comes nearly 5 years after an FDA advisory panel voted in 17P’s favor, based on results from a publicly funded, randomized, double-blind placebo-controlled trial of 463 women with at least 1 preterm delivery (N. Engl. J. Med. 2003;348:2379-85). That trial showed that women receiving weekly injections of 250 mg of 17P, starting at 20 weeks and continuing to 36 weeks or delivery, saw a 24% reduced risk of delivery before 37 weeks compared with the control group. The study also showed reductions in the rates of preterm delivery before 35 weeks and before 32 weeks in the treatment arm.

After the FDA panel’s vote in August 2006, the agency demanded further safety studies, including now-completed studies of children born to women taking 17P, from the medicine’s then-developer, which later sold its rights to 17P. In 2010 the drug’s current developer, Hologic, resubmitted its filing for 17P.

The FDA said Feb 4 that the drug’s approval comes with the manufacturer’s responsibility to complete ongoing confirmatory studies, including a new infant follow-up study, expected to end in 2018 and to include between 580 and 750 infants.

* CORRECTION, 2/17/2011: The original version of this article incorrectly stated that Makena will be marketed by Hologic, Inc. The drug will instead be marketed by Ther-Rx Corp., K-V Pharmaceutical’s branded drug subsidiary. Rights to Makena were transferred from Hologic, Inc. to K-V after the FDA approved the drug.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Photo credit: ©Vasilis Varsakelis/Fotolia.com 2

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams published online Feb. 4 in the Lancet.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

"We’ve got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects," Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers’ senior author, said in an interview. But obesity "is a serious rise that we should become serious about combating."

Dr. Ezzati and colleagues’ research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – as comprehensively and in detail as fine as possible in 199 countries and territories during 1980-2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older that were taken from published and unpublished health examination surveys and epidemiological studies (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m²), compared with 4.8% of men and 7.9% of women in 1980.

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an especially pronounced increase in the index: 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations. In Switzerland and Italy, for example, female BMI remained flat or dropped.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world’s lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women. U.K. men and women saw one of the largest drops (from 6.2 in 1980 to 5.4 in 2008).

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases, which investigators surmised resulted from dietary changes.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period.

Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

"The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects, whether it’s through lower-salt foods, or the primary care system catching and medicating," Dr. Ezzati said. "Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent."

In each paper, the teams noted that their findings were limited in some cases by data quality in some countries, particularly low- and middle-income countries for the early years of the study period. However, Dr. Ezzati noted, the three papers represented "a massive data collection exercise which has never been done before."

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, "we are either mitigating or delaying the effects of obesity – we don’t know," he said. "In the next 5-10 years, we have done all of these mitigating things but the obesity epidemic is so large and so serious it could result in diabetes being the overwhelming cardiovascular threat. In some sense [the] obesity-diabetes nexus is the wild card."

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Photo credit: ©Vasilis Varsakelis/Fotolia.com 2

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams published online Feb. 4 in the Lancet.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

"We’ve got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects," Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers’ senior author, said in an interview. But obesity "is a serious rise that we should become serious about combating."

Dr. Ezzati and colleagues’ research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – as comprehensively and in detail as fine as possible in 199 countries and territories during 1980-2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older that were taken from published and unpublished health examination surveys and epidemiological studies (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m²), compared with 4.8% of men and 7.9% of women in 1980.

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an especially pronounced increase in the index: 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations. In Switzerland and Italy, for example, female BMI remained flat or dropped.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world’s lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women. U.K. men and women saw one of the largest drops (from 6.2 in 1980 to 5.4 in 2008).

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases, which investigators surmised resulted from dietary changes.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period.

Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

"The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects, whether it’s through lower-salt foods, or the primary care system catching and medicating," Dr. Ezzati said. "Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent."

In each paper, the teams noted that their findings were limited in some cases by data quality in some countries, particularly low- and middle-income countries for the early years of the study period. However, Dr. Ezzati noted, the three papers represented "a massive data collection exercise which has never been done before."

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, "we are either mitigating or delaying the effects of obesity – we don’t know," he said. "In the next 5-10 years, we have done all of these mitigating things but the obesity epidemic is so large and so serious it could result in diabetes being the overwhelming cardiovascular threat. In some sense [the] obesity-diabetes nexus is the wild card."

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Photo credit: ©Vasilis Varsakelis/Fotolia.com 2

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams published online Feb. 4 in the Lancet.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

"We’ve got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects," Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers’ senior author, said in an interview. But obesity "is a serious rise that we should become serious about combating."

Dr. Ezzati and colleagues’ research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – as comprehensively and in detail as fine as possible in 199 countries and territories during 1980-2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older that were taken from published and unpublished health examination surveys and epidemiological studies (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m²), compared with 4.8% of men and 7.9% of women in 1980.

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an especially pronounced increase in the index: 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations. In Switzerland and Italy, for example, female BMI remained flat or dropped.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world’s lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women. U.K. men and women saw one of the largest drops (from 6.2 in 1980 to 5.4 in 2008).

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases, which investigators surmised resulted from dietary changes.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period.

Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

"The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects, whether it’s through lower-salt foods, or the primary care system catching and medicating," Dr. Ezzati said. "Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent."

In each paper, the teams noted that their findings were limited in some cases by data quality in some countries, particularly low- and middle-income countries for the early years of the study period. However, Dr. Ezzati noted, the three papers represented "a massive data collection exercise which has never been done before."

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, "we are either mitigating or delaying the effects of obesity – we don’t know," he said. "In the next 5-10 years, we have done all of these mitigating things but the obesity epidemic is so large and so serious it could result in diabetes being the overwhelming cardiovascular threat. In some sense [the] obesity-diabetes nexus is the wild card."

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Photo credit: ©Vasilis Varsakelis/Fotolia.com 2

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams published online Feb. 4 in the Lancet.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

"We’ve got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects," Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers’ senior author, said in an interview. But obesity "is a serious rise that we should become serious about combating."

Dr. Ezzati and colleagues’ research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – as comprehensively and in detail as fine as possible in 199 countries and territories during 1980-2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older that were taken from published and unpublished health examination surveys and epidemiological studies (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m²), compared with 4.8% of men and 7.9% of women in 1980.

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an especially pronounced increase in the index: 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations. In Switzerland and Italy, for example, female BMI remained flat or dropped.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world’s lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women. U.K. men and women saw one of the largest drops (from 6.2 in 1980 to 5.4 in 2008).

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases, which investigators surmised resulted from dietary changes.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period.

Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

"The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects, whether it’s through lower-salt foods, or the primary care system catching and medicating," Dr. Ezzati said. "Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent."

In each paper, the teams noted that their findings were limited in some cases by data quality in some countries, particularly low- and middle-income countries for the early years of the study period. However, Dr. Ezzati noted, the three papers represented "a massive data collection exercise which has never been done before."

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, "we are either mitigating or delaying the effects of obesity – we don’t know," he said. "In the next 5-10 years, we have done all of these mitigating things but the obesity epidemic is so large and so serious it could result in diabetes being the overwhelming cardiovascular threat. In some sense [the] obesity-diabetes nexus is the wild card."

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Photo credit: ©Vasilis Varsakelis/Fotolia.com 2

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams published online Feb. 4 in the Lancet.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

"We’ve got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects," Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers’ senior author, said in an interview. But obesity "is a serious rise that we should become serious about combating."

Dr. Ezzati and colleagues’ research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – as comprehensively and in detail as fine as possible in 199 countries and territories during 1980-2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older that were taken from published and unpublished health examination surveys and epidemiological studies (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m²), compared with 4.8% of men and 7.9% of women in 1980.

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an especially pronounced increase in the index: 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations. In Switzerland and Italy, for example, female BMI remained flat or dropped.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world’s lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women. U.K. men and women saw one of the largest drops (from 6.2 in 1980 to 5.4 in 2008).

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases, which investigators surmised resulted from dietary changes.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period.

Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

"The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects, whether it’s through lower-salt foods, or the primary care system catching and medicating," Dr. Ezzati said. "Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent."

In each paper, the teams noted that their findings were limited in some cases by data quality in some countries, particularly low- and middle-income countries for the early years of the study period. However, Dr. Ezzati noted, the three papers represented "a massive data collection exercise which has never been done before."

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, "we are either mitigating or delaying the effects of obesity – we don’t know," he said. "In the next 5-10 years, we have done all of these mitigating things but the obesity epidemic is so large and so serious it could result in diabetes being the overwhelming cardiovascular threat. In some sense [the] obesity-diabetes nexus is the wild card."

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Photo credit: ©Vasilis Varsakelis/Fotolia.com 2

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams published online Feb. 4 in the Lancet.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

"We’ve got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects," Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers’ senior author, said in an interview. But obesity "is a serious rise that we should become serious about combating."

Dr. Ezzati and colleagues’ research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – as comprehensively and in detail as fine as possible in 199 countries and territories during 1980-2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older that were taken from published and unpublished health examination surveys and epidemiological studies (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m²), compared with 4.8% of men and 7.9% of women in 1980.

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an especially pronounced increase in the index: 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations. In Switzerland and Italy, for example, female BMI remained flat or dropped.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world’s lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women. U.K. men and women saw one of the largest drops (from 6.2 in 1980 to 5.4 in 2008).

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases, which investigators surmised resulted from dietary changes.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140- 6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period.

Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

"The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects, whether it’s through lower-salt foods, or the primary care system catching and medicating," Dr. Ezzati said. "Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent."

In each paper, the teams noted that their findings were limited in some cases by data quality in some countries, particularly low- and middle-income countries for the early years of the study period. However, Dr. Ezzati noted, the three papers represented "a massive data collection exercise which has never been done before."

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, "we are either mitigating or delaying the effects of obesity – we don’t know," he said. "In the next 5-10 years, we have done all of these mitigating things but the obesity epidemic is so large and so serious it could result in diabetes being the overwhelming cardiovascular threat. In some sense [the] obesity-diabetes nexus is the wild card."

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

The Food and Drug Administration has informed the manufacturer of the weight-loss medicine combination naltrexone/bupropion that it cannot approve the drug without a new large-scale trial to establish its cardiovascular safety.

On Feb. 1, the California firm Orexigen Therapeutics, which developed naltrexone/bupropion (Contrave) along with Takeda Pharmaceutical of Japan, announced that it had received a letter from the agency saying that the drug would not be approved in advance of "a randomized, double-blind, placebo-controlled trial of sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese subjects treated with naltrexone/bupropion does not adversely affect the drug’s benefit-risk profile."

In a Feb. 1 conference call with stock analysts, Orexigen chief executive Michael A. Narachi called the agency’s decision a surprise and "a big setback" after the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-7 in December that the benefits of the drug, comprising two already-approved agents, outweighed its risks. Contrave, if approved, would have been the first new prescription antiobesity drug in the United States in a decade.

In December, the FDA advisory committee had cited concerns about elevated heart rates and systolic and diastolic blood pressure among the more than 4,000 obese patients, most of them women, who took part in phase III clinical trials. Mr. Narachi said that the FDA’s move stemmed not from any new analysis or data on cardiovascular events submitted since December but rather the same "small but consistent increase in blood pressure and heart rate" discussed at that meeting.

In studies submitted to the FDA by the manufacturer, after 56 weeks, those on the proposed dose (32 mg of naltrexone plus 360 mg bupropion per day, taken in two divided doses) lost 5%-8% of their baseline body weight, compared with a loss of 1%-2% in those on placebo. The proportion of those who lost at least 5% of their baseline body weight ranged from 45% to 56% of those on the proposed dose, compared with 16%-43% of those on placebo.

However, a quarter of people treated with naltrexone/bupropion had significant increases in systolic blood pressure of at least 10% over baseline, compared with less than a fifth of those in the control arms, and increases of diastolic blood pressure of at least 5 mm/Hg over baseline in 37% of those on the combination, compared with 29% of those on placebo. Regarding heart rate, 26% of patients in the treatment arms had increases in heart rate of at least 10 beats per minute over baseline, compared with 19% of those on placebo.

The panelists at the December FDA meeting who agreed that the potential benefits outweighed the potential risks said that the drug combination had met one of two criteria set by the FDA for being an effective weight-loss agent, and cited the extensive clinical experience with the two drugs and the company’s commitment to conduct a postmarketing long-term safety and efficacy study, which would also evaluate the risk for major cardiac events.

Mr. Narachi said on Feb. 1 that until the company begins talks with the agency, it cannot predict what the cardiovascular safety trial design might look like or whether the company would even proceed with such a trial, as cardiovascular safety trials require large numbers of patients and can last 4-5 years. "We’ll be doing what’s in the best interest of our shareholders," he said.

Contrave, containing the antidepressant bupropion and the drug- and alcohol-addiction treatment naltrexone, is one of two medications developed by Orexigen for obesity; the other, called Empatic, has completed phase IIb trials. Empatic is also a combination of two already-approved mediations, the anticonvulsant zonisamide and bupropion.

Internal Medicine News Digital Network reporter Elizabeth Mechcatie contributed to this story.

The Food and Drug Administration has informed the manufacturer of the weight-loss medicine combination naltrexone/bupropion that it cannot approve the drug without a new large-scale trial to establish its cardiovascular safety.

On Feb. 1, the California firm Orexigen Therapeutics, which developed naltrexone/bupropion (Contrave) along with Takeda Pharmaceutical of Japan, announced that it had received a letter from the agency saying that the drug would not be approved in advance of "a randomized, double-blind, placebo-controlled trial of sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese subjects treated with naltrexone/bupropion does not adversely affect the drug’s benefit-risk profile."

In a Feb. 1 conference call with stock analysts, Orexigen chief executive Michael A. Narachi called the agency’s decision a surprise and "a big setback" after the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-7 in December that the benefits of the drug, comprising two already-approved agents, outweighed its risks. Contrave, if approved, would have been the first new prescription antiobesity drug in the United States in a decade.

In December, the FDA advisory committee had cited concerns about elevated heart rates and systolic and diastolic blood pressure among the more than 4,000 obese patients, most of them women, who took part in phase III clinical trials. Mr. Narachi said that the FDA’s move stemmed not from any new analysis or data on cardiovascular events submitted since December but rather the same "small but consistent increase in blood pressure and heart rate" discussed at that meeting.

In studies submitted to the FDA by the manufacturer, after 56 weeks, those on the proposed dose (32 mg of naltrexone plus 360 mg bupropion per day, taken in two divided doses) lost 5%-8% of their baseline body weight, compared with a loss of 1%-2% in those on placebo. The proportion of those who lost at least 5% of their baseline body weight ranged from 45% to 56% of those on the proposed dose, compared with 16%-43% of those on placebo.

However, a quarter of people treated with naltrexone/bupropion had significant increases in systolic blood pressure of at least 10% over baseline, compared with less than a fifth of those in the control arms, and increases of diastolic blood pressure of at least 5 mm/Hg over baseline in 37% of those on the combination, compared with 29% of those on placebo. Regarding heart rate, 26% of patients in the treatment arms had increases in heart rate of at least 10 beats per minute over baseline, compared with 19% of those on placebo.

The panelists at the December FDA meeting who agreed that the potential benefits outweighed the potential risks said that the drug combination had met one of two criteria set by the FDA for being an effective weight-loss agent, and cited the extensive clinical experience with the two drugs and the company’s commitment to conduct a postmarketing long-term safety and efficacy study, which would also evaluate the risk for major cardiac events.

Mr. Narachi said on Feb. 1 that until the company begins talks with the agency, it cannot predict what the cardiovascular safety trial design might look like or whether the company would even proceed with such a trial, as cardiovascular safety trials require large numbers of patients and can last 4-5 years. "We’ll be doing what’s in the best interest of our shareholders," he said.

Contrave, containing the antidepressant bupropion and the drug- and alcohol-addiction treatment naltrexone, is one of two medications developed by Orexigen for obesity; the other, called Empatic, has completed phase IIb trials. Empatic is also a combination of two already-approved mediations, the anticonvulsant zonisamide and bupropion.

Internal Medicine News Digital Network reporter Elizabeth Mechcatie contributed to this story.

The Food and Drug Administration has informed the manufacturer of the weight-loss medicine combination naltrexone/bupropion that it cannot approve the drug without a new large-scale trial to establish its cardiovascular safety.

On Feb. 1, the California firm Orexigen Therapeutics, which developed naltrexone/bupropion (Contrave) along with Takeda Pharmaceutical of Japan, announced that it had received a letter from the agency saying that the drug would not be approved in advance of "a randomized, double-blind, placebo-controlled trial of sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese subjects treated with naltrexone/bupropion does not adversely affect the drug’s benefit-risk profile."

In a Feb. 1 conference call with stock analysts, Orexigen chief executive Michael A. Narachi called the agency’s decision a surprise and "a big setback" after the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-7 in December that the benefits of the drug, comprising two already-approved agents, outweighed its risks. Contrave, if approved, would have been the first new prescription antiobesity drug in the United States in a decade.

In December, the FDA advisory committee had cited concerns about elevated heart rates and systolic and diastolic blood pressure among the more than 4,000 obese patients, most of them women, who took part in phase III clinical trials. Mr. Narachi said that the FDA’s move stemmed not from any new analysis or data on cardiovascular events submitted since December but rather the same "small but consistent increase in blood pressure and heart rate" discussed at that meeting.

In studies submitted to the FDA by the manufacturer, after 56 weeks, those on the proposed dose (32 mg of naltrexone plus 360 mg bupropion per day, taken in two divided doses) lost 5%-8% of their baseline body weight, compared with a loss of 1%-2% in those on placebo. The proportion of those who lost at least 5% of their baseline body weight ranged from 45% to 56% of those on the proposed dose, compared with 16%-43% of those on placebo.

However, a quarter of people treated with naltrexone/bupropion had significant increases in systolic blood pressure of at least 10% over baseline, compared with less than a fifth of those in the control arms, and increases of diastolic blood pressure of at least 5 mm/Hg over baseline in 37% of those on the combination, compared with 29% of those on placebo. Regarding heart rate, 26% of patients in the treatment arms had increases in heart rate of at least 10 beats per minute over baseline, compared with 19% of those on placebo.

The panelists at the December FDA meeting who agreed that the potential benefits outweighed the potential risks said that the drug combination had met one of two criteria set by the FDA for being an effective weight-loss agent, and cited the extensive clinical experience with the two drugs and the company’s commitment to conduct a postmarketing long-term safety and efficacy study, which would also evaluate the risk for major cardiac events.

Mr. Narachi said on Feb. 1 that until the company begins talks with the agency, it cannot predict what the cardiovascular safety trial design might look like or whether the company would even proceed with such a trial, as cardiovascular safety trials require large numbers of patients and can last 4-5 years. "We’ll be doing what’s in the best interest of our shareholders," he said.

Contrave, containing the antidepressant bupropion and the drug- and alcohol-addiction treatment naltrexone, is one of two medications developed by Orexigen for obesity; the other, called Empatic, has completed phase IIb trials. Empatic is also a combination of two already-approved mediations, the anticonvulsant zonisamide and bupropion.

Internal Medicine News Digital Network reporter Elizabeth Mechcatie contributed to this story.

The Food and Drug Administration has informed the manufacturer of the weight-loss medicine combination naltrexone/bupropion that it cannot approve the drug without a new large-scale trial to establish its cardiovascular safety.

On Feb. 1, the California firm Orexigen Therapeutics, which developed naltrexone/bupropion (Contrave) along with Takeda Pharmaceutical of Japan, announced that it had received a letter from the agency saying that the drug would not be approved in advance of "a randomized, double-blind, placebo-controlled trial of sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese subjects treated with naltrexone/bupropion does not adversely affect the drug’s benefit-risk profile."

In a Feb. 1 conference call with stock analysts, Orexigen chief executive Michael A. Narachi called the agency’s decision a surprise and "a big setback" after the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-7 in December that the benefits of the drug, comprising two already-approved agents, outweighed its risks. Contrave, if approved, would have been the first new prescription antiobesity drug in the United States in a decade.

In December, the FDA advisory committee had cited concerns about elevated heart rates and systolic and diastolic blood pressure among the more than 4,000 obese patients, most of them women, who took part in phase III clinical trials. Mr. Narachi said that the FDA’s move stemmed not from any new analysis or data on cardiovascular events submitted since December but rather the same "small but consistent increase in blood pressure and heart rate" discussed at that meeting.

In studies submitted to the FDA by the manufacturer, after 56 weeks, those on the proposed dose (32 mg of naltrexone plus 360 mg bupropion per day, taken in two divided doses) lost 5%-8% of their baseline body weight, compared with a loss of 1%-2% in those on placebo. The proportion of those who lost at least 5% of their baseline body weight ranged from 45% to 56% of those on the proposed dose, compared with 16%-43% of those on placebo.

However, a quarter of people treated with naltrexone/bupropion had significant increases in systolic blood pressure of at least 10% over baseline, compared with less than a fifth of those in the control arms, and increases of diastolic blood pressure of at least 5 mm/Hg over baseline in 37% of those on the combination, compared with 29% of those on placebo. Regarding heart rate, 26% of patients in the treatment arms had increases in heart rate of at least 10 beats per minute over baseline, compared with 19% of those on placebo.

The panelists at the December FDA meeting who agreed that the potential benefits outweighed the potential risks said that the drug combination had met one of two criteria set by the FDA for being an effective weight-loss agent, and cited the extensive clinical experience with the two drugs and the company’s commitment to conduct a postmarketing long-term safety and efficacy study, which would also evaluate the risk for major cardiac events.

Mr. Narachi said on Feb. 1 that until the company begins talks with the agency, it cannot predict what the cardiovascular safety trial design might look like or whether the company would even proceed with such a trial, as cardiovascular safety trials require large numbers of patients and can last 4-5 years. "We’ll be doing what’s in the best interest of our shareholders," he said.

Contrave, containing the antidepressant bupropion and the drug- and alcohol-addiction treatment naltrexone, is one of two medications developed by Orexigen for obesity; the other, called Empatic, has completed phase IIb trials. Empatic is also a combination of two already-approved mediations, the anticonvulsant zonisamide and bupropion.

Internal Medicine News Digital Network reporter Elizabeth Mechcatie contributed to this story.

The Food and Drug Administration has informed the manufacturer of the weight-loss medicine combination naltrexone/bupropion that it cannot approve the drug without a new large-scale trial to establish its cardiovascular safety.

On Feb. 1, the California firm Orexigen Therapeutics, which developed naltrexone/bupropion (Contrave) along with Takeda Pharmaceutical of Japan, announced that it had received a letter from the agency saying that the drug would not be approved in advance of "a randomized, double-blind, placebo-controlled trial of sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese subjects treated with naltrexone/bupropion does not adversely affect the drug’s benefit-risk profile."

In a Feb. 1 conference call with stock analysts, Orexigen chief executive Michael A. Narachi called the agency’s decision a surprise and "a big setback" after the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-7 in December that the benefits of the drug, comprising two already-approved agents, outweighed its risks. Contrave, if approved, would have been the first new prescription antiobesity drug in the United States in a decade.

In December, the FDA advisory committee had cited concerns about elevated heart rates and systolic and diastolic blood pressure among the more than 4,000 obese patients, most of them women, who took part in phase III clinical trials. Mr. Narachi said that the FDA’s move stemmed not from any new analysis or data on cardiovascular events submitted since December but rather the same "small but consistent increase in blood pressure and heart rate" discussed at that meeting.

In studies submitted to the FDA by the manufacturer, after 56 weeks, those on the proposed dose (32 mg of naltrexone plus 360 mg bupropion per day, taken in two divided doses) lost 5%-8% of their baseline body weight, compared with a loss of 1%-2% in those on placebo. The proportion of those who lost at least 5% of their baseline body weight ranged from 45% to 56% of those on the proposed dose, compared with 16%-43% of those on placebo.

However, a quarter of people treated with naltrexone/bupropion had significant increases in systolic blood pressure of at least 10% over baseline, compared with less than a fifth of those in the control arms, and increases of diastolic blood pressure of at least 5 mm/Hg over baseline in 37% of those on the combination, compared with 29% of those on placebo. Regarding heart rate, 26% of patients in the treatment arms had increases in heart rate of at least 10 beats per minute over baseline, compared with 19% of those on placebo.

The panelists at the December FDA meeting who agreed that the potential benefits outweighed the potential risks said that the drug combination had met one of two criteria set by the FDA for being an effective weight-loss agent, and cited the extensive clinical experience with the two drugs and the company’s commitment to conduct a postmarketing long-term safety and efficacy study, which would also evaluate the risk for major cardiac events.

Mr. Narachi said on Feb. 1 that until the company begins talks with the agency, it cannot predict what the cardiovascular safety trial design might look like or whether the company would even proceed with such a trial, as cardiovascular safety trials require large numbers of patients and can last 4-5 years. "We’ll be doing what’s in the best interest of our shareholders," he said.

Contrave, containing the antidepressant bupropion and the drug- and alcohol-addiction treatment naltrexone, is one of two medications developed by Orexigen for obesity; the other, called Empatic, has completed phase IIb trials. Empatic is also a combination of two already-approved mediations, the anticonvulsant zonisamide and bupropion.

Internal Medicine News Digital Network reporter Elizabeth Mechcatie contributed to this story.

The Food and Drug Administration has informed the manufacturer of the weight-loss medicine combination naltrexone/bupropion that it cannot approve the drug without a new large-scale trial to establish its cardiovascular safety.

On Feb. 1, the California firm Orexigen Therapeutics, which developed naltrexone/bupropion (Contrave) along with Takeda Pharmaceutical of Japan, announced that it had received a letter from the agency saying that the drug would not be approved in advance of "a randomized, double-blind, placebo-controlled trial of sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese subjects treated with naltrexone/bupropion does not adversely affect the drug’s benefit-risk profile."

In a Feb. 1 conference call with stock analysts, Orexigen chief executive Michael A. Narachi called the agency’s decision a surprise and "a big setback" after the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-7 in December that the benefits of the drug, comprising two already-approved agents, outweighed its risks. Contrave, if approved, would have been the first new prescription antiobesity drug in the United States in a decade.

In December, the FDA advisory committee had cited concerns about elevated heart rates and systolic and diastolic blood pressure among the more than 4,000 obese patients, most of them women, who took part in phase III clinical trials. Mr. Narachi said that the FDA’s move stemmed not from any new analysis or data on cardiovascular events submitted since December but rather the same "small but consistent increase in blood pressure and heart rate" discussed at that meeting.

In studies submitted to the FDA by the manufacturer, after 56 weeks, those on the proposed dose (32 mg of naltrexone plus 360 mg bupropion per day, taken in two divided doses) lost 5%-8% of their baseline body weight, compared with a loss of 1%-2% in those on placebo. The proportion of those who lost at least 5% of their baseline body weight ranged from 45% to 56% of those on the proposed dose, compared with 16%-43% of those on placebo.

However, a quarter of people treated with naltrexone/bupropion had significant increases in systolic blood pressure of at least 10% over baseline, compared with less than a fifth of those in the control arms, and increases of diastolic blood pressure of at least 5 mm/Hg over baseline in 37% of those on the combination, compared with 29% of those on placebo. Regarding heart rate, 26% of patients in the treatment arms had increases in heart rate of at least 10 beats per minute over baseline, compared with 19% of those on placebo.

The panelists at the December FDA meeting who agreed that the potential benefits outweighed the potential risks said that the drug combination had met one of two criteria set by the FDA for being an effective weight-loss agent, and cited the extensive clinical experience with the two drugs and the company’s commitment to conduct a postmarketing long-term safety and efficacy study, which would also evaluate the risk for major cardiac events.

Mr. Narachi said on Feb. 1 that until the company begins talks with the agency, it cannot predict what the cardiovascular safety trial design might look like or whether the company would even proceed with such a trial, as cardiovascular safety trials require large numbers of patients and can last 4-5 years. "We’ll be doing what’s in the best interest of our shareholders," he said.

Contrave, containing the antidepressant bupropion and the drug- and alcohol-addiction treatment naltrexone, is one of two medications developed by Orexigen for obesity; the other, called Empatic, has completed phase IIb trials. Empatic is also a combination of two already-approved mediations, the anticonvulsant zonisamide and bupropion.

Internal Medicine News Digital Network reporter Elizabeth Mechcatie contributed to this story.

People with type 2 diabetes should undergo strength training two or three times a week, get at least 150 minutes of aerobic exercise per week, and go no more than 2 consecutive days without a workout, according to new guidelines on exercise in diabetes – the first in 10 years – from the American College of Sports Medicine and the American Diabetes Association.

“It is now well established that participation in regular [physical activity] improves blood glucose control and can prevent or delay [type 2 diabetes], along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life,” the groups wrote in the introduction to the new guidelines (Med. Sci. Sports Exerc. 2010;42:2282-303).

The guidelines were produced using results from nearly 300 studies, the vast majority of them published within the past decade. While the ACSM and ADA's 2000 guidelines had also emphasized aerobic exercise, the strength recommendations are new, said Sheri Colberg-Ochs, Ph.D., of Old Dominion University in Norfolk, Va., a member of the ACSM and a coauthor of the guidelines.

“You can see some really dramatic improvements in glucose control with resistance training,” Dr. Colberg-Ochs said in an interview. And the combined exercise may be better still: A recent study of sedentary men and women with type 2 diabetes (n = 262), which was published too late to be considered in crafting the guidelines, showed that a combination of aerobic and resistance training improved hemoglobin A_1c levels better than did either aerobic or resistance training alone, Dr. Colbert-Ochs noted (JAMA 2010;304:2298-9.)

Many of the exercise benefits described in the guidelines are independent of weight loss, and indeed the guidelines' authors noted that the exercise requirements alone were probably insufficient to produce significant weight change. But they also emphasized that even highly overweight and sedentary people need to be encouraged to exercise, as the benefits of exercise for type 2 diabetes far outweigh known risks.

Though people with high cardiovascular risk factors would benefit from a physician evaluation before starting to exercise, the authors said, most people do not need to consult a doctor before beginning a modest program of brisk walking, for example, Dr. Colberg-Ochs said. “To tell people to go to their doctor gives them the wrong impression – that exercise is dangerous – and sets up an unnecessary barrier. So we relaxed the recommendation” in the new guidelines, she said.

That said, Dr. Colbert-Ochs added, people must be eased into an exercise program. “You would not just get someone off the couch and say go get 150 minutes – that would be ridiculous. One of the things I personally prescribe is small lifestyle changes. Just getting people moving around and taking more steps starts to build some basic endurance.”

Dr. Colberg-Ochs said that the guideline had recommended 150 minutes of aerobic activity plus two or three weight workouts per week because “most of the existing studies were limited in that they only looked at certain amounts of time. The only thing we could say for sure is there wasn't enough evidence telling people they could do less.”

For resistance training, the authors wrote, each session “should minimally include 5-10 exercises involving the major muscle groups (in the upper body, lower body, and core) and involve completion of 10-15 repetitions to near fatigue per set early in training progressing over time to heavier weights (or resistance) that can be lifted only 8-10 times.”

Aerobic training means working at between 40% and 60% of maximal aerobic capacity, which in many people is achieved by brisk walking, the authors wrote. The guidelines also promoted increasing unstructured daily movement, including the use of a pedometer, but viewed flexibility training as an add-on and not a substitute for aerobic training and weights. Tai chi and yoga were excluded from the recommendations for thus-far insufficient evidence of benefit in preventing or controlling type 2 diabetes.

The guidelines also reported that for people with type 2 diabetes:

▸ Aerobic training may slightly reduce systolic blood pressure, but reductions in diastolic BP are less common.

▸ Supervised training resulted in greater compliance and blood glucose control than did unsupervised training.

▸ Blood lipid responses to training are mixed, but may result in a small reduction in LDL cholesterol with no change in HDL cholesterol or triglycerides. Combined weight loss and exercise may be more effective than exercise alone.

▸ Increased exercise can reduce symptoms of depression and improve health-related quality of life.

▸ Exercise is possible when blood glucose levels exceed 300 mg/dL without ketosis, provided the patient is feeling well and is adequately hydrated.

▸ Medication dosage adjustments to prevent exercise-associated hypoglycemia may be required by individuals using insulin or certain insulin secretagogues. Other medications prescribed for concomitant health problems do not affect exercise, with the exception of beta-blockers, some diuretics, and statins.

Neither Dr. Colberg-Ochs nor her coauthors declared conflicts of interest.

People with type 2 diabetes should undergo strength training two or three times a week, get at least 150 minutes of aerobic exercise per week, and go no more than 2 consecutive days without a workout, according to new guidelines on exercise in diabetes – the first in 10 years – from the American College of Sports Medicine and the American Diabetes Association.

“It is now well established that participation in regular [physical activity] improves blood glucose control and can prevent or delay [type 2 diabetes], along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life,” the groups wrote in the introduction to the new guidelines (Med. Sci. Sports Exerc. 2010;42:2282-303).

The guidelines were produced using results from nearly 300 studies, the vast majority of them published within the past decade. While the ACSM and ADA's 2000 guidelines had also emphasized aerobic exercise, the strength recommendations are new, said Sheri Colberg-Ochs, Ph.D., of Old Dominion University in Norfolk, Va., a member of the ACSM and a coauthor of the guidelines.

“You can see some really dramatic improvements in glucose control with resistance training,” Dr. Colberg-Ochs said in an interview. And the combined exercise may be better still: A recent study of sedentary men and women with type 2 diabetes (n = 262), which was published too late to be considered in crafting the guidelines, showed that a combination of aerobic and resistance training improved hemoglobin A_1c levels better than did either aerobic or resistance training alone, Dr. Colbert-Ochs noted (JAMA 2010;304:2298-9.)

Many of the exercise benefits described in the guidelines are independent of weight loss, and indeed the guidelines' authors noted that the exercise requirements alone were probably insufficient to produce significant weight change. But they also emphasized that even highly overweight and sedentary people need to be encouraged to exercise, as the benefits of exercise for type 2 diabetes far outweigh known risks.

Though people with high cardiovascular risk factors would benefit from a physician evaluation before starting to exercise, the authors said, most people do not need to consult a doctor before beginning a modest program of brisk walking, for example, Dr. Colberg-Ochs said. “To tell people to go to their doctor gives them the wrong impression – that exercise is dangerous – and sets up an unnecessary barrier. So we relaxed the recommendation” in the new guidelines, she said.

That said, Dr. Colbert-Ochs added, people must be eased into an exercise program. “You would not just get someone off the couch and say go get 150 minutes – that would be ridiculous. One of the things I personally prescribe is small lifestyle changes. Just getting people moving around and taking more steps starts to build some basic endurance.”

Dr. Colberg-Ochs said that the guideline had recommended 150 minutes of aerobic activity plus two or three weight workouts per week because “most of the existing studies were limited in that they only looked at certain amounts of time. The only thing we could say for sure is there wasn't enough evidence telling people they could do less.”

For resistance training, the authors wrote, each session “should minimally include 5-10 exercises involving the major muscle groups (in the upper body, lower body, and core) and involve completion of 10-15 repetitions to near fatigue per set early in training progressing over time to heavier weights (or resistance) that can be lifted only 8-10 times.”

Aerobic training means working at between 40% and 60% of maximal aerobic capacity, which in many people is achieved by brisk walking, the authors wrote. The guidelines also promoted increasing unstructured daily movement, including the use of a pedometer, but viewed flexibility training as an add-on and not a substitute for aerobic training and weights. Tai chi and yoga were excluded from the recommendations for thus-far insufficient evidence of benefit in preventing or controlling type 2 diabetes.

The guidelines also reported that for people with type 2 diabetes:

▸ Aerobic training may slightly reduce systolic blood pressure, but reductions in diastolic BP are less common.

▸ Supervised training resulted in greater compliance and blood glucose control than did unsupervised training.

▸ Blood lipid responses to training are mixed, but may result in a small reduction in LDL cholesterol with no change in HDL cholesterol or triglycerides. Combined weight loss and exercise may be more effective than exercise alone.

▸ Increased exercise can reduce symptoms of depression and improve health-related quality of life.

▸ Exercise is possible when blood glucose levels exceed 300 mg/dL without ketosis, provided the patient is feeling well and is adequately hydrated.

▸ Medication dosage adjustments to prevent exercise-associated hypoglycemia may be required by individuals using insulin or certain insulin secretagogues. Other medications prescribed for concomitant health problems do not affect exercise, with the exception of beta-blockers, some diuretics, and statins.

Neither Dr. Colberg-Ochs nor her coauthors declared conflicts of interest.

People with type 2 diabetes should undergo strength training two or three times a week, get at least 150 minutes of aerobic exercise per week, and go no more than 2 consecutive days without a workout, according to new guidelines on exercise in diabetes – the first in 10 years – from the American College of Sports Medicine and the American Diabetes Association.

“It is now well established that participation in regular [physical activity] improves blood glucose control and can prevent or delay [type 2 diabetes], along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life,” the groups wrote in the introduction to the new guidelines (Med. Sci. Sports Exerc. 2010;42:2282-303).

The guidelines were produced using results from nearly 300 studies, the vast majority of them published within the past decade. While the ACSM and ADA's 2000 guidelines had also emphasized aerobic exercise, the strength recommendations are new, said Sheri Colberg-Ochs, Ph.D., of Old Dominion University in Norfolk, Va., a member of the ACSM and a coauthor of the guidelines.

“You can see some really dramatic improvements in glucose control with resistance training,” Dr. Colberg-Ochs said in an interview. And the combined exercise may be better still: A recent study of sedentary men and women with type 2 diabetes (n = 262), which was published too late to be considered in crafting the guidelines, showed that a combination of aerobic and resistance training improved hemoglobin A_1c levels better than did either aerobic or resistance training alone, Dr. Colbert-Ochs noted (JAMA 2010;304:2298-9.)

Many of the exercise benefits described in the guidelines are independent of weight loss, and indeed the guidelines' authors noted that the exercise requirements alone were probably insufficient to produce significant weight change. But they also emphasized that even highly overweight and sedentary people need to be encouraged to exercise, as the benefits of exercise for type 2 diabetes far outweigh known risks.

Though people with high cardiovascular risk factors would benefit from a physician evaluation before starting to exercise, the authors said, most people do not need to consult a doctor before beginning a modest program of brisk walking, for example, Dr. Colberg-Ochs said. “To tell people to go to their doctor gives them the wrong impression – that exercise is dangerous – and sets up an unnecessary barrier. So we relaxed the recommendation” in the new guidelines, she said.

That said, Dr. Colbert-Ochs added, people must be eased into an exercise program. “You would not just get someone off the couch and say go get 150 minutes – that would be ridiculous. One of the things I personally prescribe is small lifestyle changes. Just getting people moving around and taking more steps starts to build some basic endurance.”

Dr. Colberg-Ochs said that the guideline had recommended 150 minutes of aerobic activity plus two or three weight workouts per week because “most of the existing studies were limited in that they only looked at certain amounts of time. The only thing we could say for sure is there wasn't enough evidence telling people they could do less.”

For resistance training, the authors wrote, each session “should minimally include 5-10 exercises involving the major muscle groups (in the upper body, lower body, and core) and involve completion of 10-15 repetitions to near fatigue per set early in training progressing over time to heavier weights (or resistance) that can be lifted only 8-10 times.”

Aerobic training means working at between 40% and 60% of maximal aerobic capacity, which in many people is achieved by brisk walking, the authors wrote. The guidelines also promoted increasing unstructured daily movement, including the use of a pedometer, but viewed flexibility training as an add-on and not a substitute for aerobic training and weights. Tai chi and yoga were excluded from the recommendations for thus-far insufficient evidence of benefit in preventing or controlling type 2 diabetes.

The guidelines also reported that for people with type 2 diabetes:

▸ Aerobic training may slightly reduce systolic blood pressure, but reductions in diastolic BP are less common.

▸ Supervised training resulted in greater compliance and blood glucose control than did unsupervised training.

▸ Blood lipid responses to training are mixed, but may result in a small reduction in LDL cholesterol with no change in HDL cholesterol or triglycerides. Combined weight loss and exercise may be more effective than exercise alone.

▸ Increased exercise can reduce symptoms of depression and improve health-related quality of life.

▸ Exercise is possible when blood glucose levels exceed 300 mg/dL without ketosis, provided the patient is feeling well and is adequately hydrated.

▸ Medication dosage adjustments to prevent exercise-associated hypoglycemia may be required by individuals using insulin or certain insulin secretagogues. Other medications prescribed for concomitant health problems do not affect exercise, with the exception of beta-blockers, some diuretics, and statins.

Neither Dr. Colberg-Ochs nor her coauthors declared conflicts of interest.

More than a decade after issuing its first report on suicides in hospitals, the Joint Commission has followed up with a new one, reminding clinicians that suicides and suicide attempts can occur anywhere – not just in psychiatric units.

But emergency physicians say that suicides in nonpsychiatric units are part of a broader and more difficult problem to solve: a lack of appropriate care for psychiatric patients that forces other units – particularly emergency departments – to hold these patients in environments not designed for their safety.

Since 1995, the commission wrote, there have been 827 reports of patient suicides, 14% of which occurred in nonpsychiatric settings, more than half of these in emergency departments. The 827 cases represented only those voluntarily reported, the commission noted, and therefore is likely an undercount.

The suicides occurred in bathrooms, bedrooms, closets, showers, or just after patients left the hospital against medical advice. Patients hung, shot, lacerated, or asphyxiated themselves, jumped from high places, or ingested drugs. A number of suicides were carried out using materials immediately available in the hospital – bell cords, bandages, sheets, plastic bags, or elastic tubing.

Many patients who attempt suicide in hospitals are at unknown risk for suicide, and often lack a known psychiatric history, the commission noted. A number of measures that hospitals can take to become more vigilant about prevention were recommended in the report. These measures include intensifying screening of new patients, having volunteer or family "sitters" assigned to at-risk patients, improving communication during handoffs, and empowering staff to take preemptive actions.

Dr. Sandra M. Schneider, attending physician at Strong Memorial Hospital in Rochester, N.Y., and current president of the American College of Emergency Physicians, said she welcomed the Joint Commission report as a "wake-up call" to provide more intensive screening to identify at-risk patients without psychiatric histories, including people who have had a recent stroke or heart attack and who can suddenly and temporarily be vulnerable to suicidal thoughts.

However, Dr. Schneider said, better screening can solve only part of the problem. "Many hospitals are boarding or holding psychiatric patients until a bed becomes available," she said in an interview. "The bigger problem is access to timely care of these patients, and the ED is just not the best environment for them."

Dr. David J. Mendelson, an emergency physician and vice president of Medical Affairs for EmCare Inc. in Dallas, agreed. "I have nothing against the recommendations to better equip the doctors and staff to screen the patients," Dr. Mendelson said in an interview. "We do that anyway, though it’s not formalized." Nonetheless, he said, the Joint Commission findings "do not address the core problem."

Dr. Mendelson was the lead author of a 2008 survey for the American College of Emergency Physicians on the problem of psychiatric boarding, a perennial issue in EDs.

Of the survey’s 328 respondents – all ED physicians and most of them ED directors or department chairs – 79% said psychiatric patients were boarded in their EDs, with a third of the patients boarded for 6 hours or more; 62% said these patients received no psychiatric services while they were being boarded. Since 2008, Dr. Mendelson said, the problem seems to have only gotten worse, "probably because of the economy and because we’re seeing fewer patients in EDs with any sort of insurance at all."

A new nationwide survey of 603 hospital ED administrators by the Schumacher Group found that 56% of EDs are often unable to transfer mental/behavioral patients to inpatient facilities in a timely manner, and 30% are sometimes unable to do so. Only 3% reported always being able to transfer mental/behavioral patients in a timely manner. Boarding times of 12 hours or less were reported by 29% of EDs, 30% said the longest they boarded these patients was 24 hours, 20% reported waits of as long as 2 days, 11% had boarded them for up to 5 days, and 10% had boarded mental/behavioral patients for more than a week.

"The mental health problem in America is being swept under the rug for hospital emergency departments to deal with," Dr. William Schumacher, CEO of the Schumacher Group, said in a statement.

Dr. Schneider said that the process of finding a bed for a psychiatric patient can take days, and that "even though we take great precautions, the emergency department does not have a protected environment for patients who might be interested in committing suicide." Once, she said, "we had a patient who tried to commit suicide by drinking the hand sanitizer. What are we supposed to do? Can we really get rid of the hand sanitizer?"

The American College of Emergency Physicians has published several policy papers in recent years addressing the issue of psychiatric patients presenting to emergency departments in lieu of a psychiatric care facility. Dr. Mendelson said that solving the suicide problem is partly a matter of resources, and that until these problems can be solved, "the fact that there are bad things happening" is not a surprise. "We need more money, especially more federal money, to deal with this," he said.

Dr. Schneider said that her hospital is fortunate to have a psychiatric department adjacent to its emergency department, social workers who screen every patient over age 70 – older male patients are at highest risk for suicide – and a psychiatric resident available much of the time. Most hospitals "would not have a psychiatrist or psychiatric nurse on duty and would not have immediate access to a psychiatric bed," she said. "But even we will hold these patients in the ED weekends or nights," she said.

Some of the ways Dr. Schneider and her team keep patients safe in the meantime, she said, involve "colored clothes and footies" that indicate to staff and guards an at-risk patient. Staff take evaluations from the friends of young patients who might not be candid about suicidal feelings. And any input from a paramedic with concerns about the state of a patient’s home is taken seriously.

The important thing, she said, is that all members of the emergency department team are empowered to act. "In emergency medicine, we believe everyone on the team can push the button. Anyone can come to the physician or nurse and say, ‘I’m worried about the patient in room 120.’ This is a team sport."

More than a decade after issuing its first report on suicides in hospitals, the Joint Commission has followed up with a new one, reminding clinicians that suicides and suicide attempts can occur anywhere – not just in psychiatric units.

But emergency physicians say that suicides in nonpsychiatric units are part of a broader and more difficult problem to solve: a lack of appropriate care for psychiatric patients that forces other units – particularly emergency departments – to hold these patients in environments not designed for their safety.

Since 1995, the commission wrote, there have been 827 reports of patient suicides, 14% of which occurred in nonpsychiatric settings, more than half of these in emergency departments. The 827 cases represented only those voluntarily reported, the commission noted, and therefore is likely an undercount.

The suicides occurred in bathrooms, bedrooms, closets, showers, or just after patients left the hospital against medical advice. Patients hung, shot, lacerated, or asphyxiated themselves, jumped from high places, or ingested drugs. A number of suicides were carried out using materials immediately available in the hospital – bell cords, bandages, sheets, plastic bags, or elastic tubing.

Many patients who attempt suicide in hospitals are at unknown risk for suicide, and often lack a known psychiatric history, the commission noted. A number of measures that hospitals can take to become more vigilant about prevention were recommended in the report. These measures include intensifying screening of new patients, having volunteer or family "sitters" assigned to at-risk patients, improving communication during handoffs, and empowering staff to take preemptive actions.

Dr. Sandra M. Schneider, attending physician at Strong Memorial Hospital in Rochester, N.Y., and current president of the American College of Emergency Physicians, said she welcomed the Joint Commission report as a "wake-up call" to provide more intensive screening to identify at-risk patients without psychiatric histories, including people who have had a recent stroke or heart attack and who can suddenly and temporarily be vulnerable to suicidal thoughts.

However, Dr. Schneider said, better screening can solve only part of the problem. "Many hospitals are boarding or holding psychiatric patients until a bed becomes available," she said in an interview. "The bigger problem is access to timely care of these patients, and the ED is just not the best environment for them."

Dr. David J. Mendelson, an emergency physician and vice president of Medical Affairs for EmCare Inc. in Dallas, agreed. "I have nothing against the recommendations to better equip the doctors and staff to screen the patients," Dr. Mendelson said in an interview. "We do that anyway, though it’s not formalized." Nonetheless, he said, the Joint Commission findings "do not address the core problem."

Dr. Mendelson was the lead author of a 2008 survey for the American College of Emergency Physicians on the problem of psychiatric boarding, a perennial issue in EDs.

Of the survey’s 328 respondents – all ED physicians and most of them ED directors or department chairs – 79% said psychiatric patients were boarded in their EDs, with a third of the patients boarded for 6 hours or more; 62% said these patients received no psychiatric services while they were being boarded. Since 2008, Dr. Mendelson said, the problem seems to have only gotten worse, "probably because of the economy and because we’re seeing fewer patients in EDs with any sort of insurance at all."

A new nationwide survey of 603 hospital ED administrators by the Schumacher Group found that 56% of EDs are often unable to transfer mental/behavioral patients to inpatient facilities in a timely manner, and 30% are sometimes unable to do so. Only 3% reported always being able to transfer mental/behavioral patients in a timely manner. Boarding times of 12 hours or less were reported by 29% of EDs, 30% said the longest they boarded these patients was 24 hours, 20% reported waits of as long as 2 days, 11% had boarded them for up to 5 days, and 10% had boarded mental/behavioral patients for more than a week.

"The mental health problem in America is being swept under the rug for hospital emergency departments to deal with," Dr. William Schumacher, CEO of the Schumacher Group, said in a statement.

Dr. Schneider said that the process of finding a bed for a psychiatric patient can take days, and that "even though we take great precautions, the emergency department does not have a protected environment for patients who might be interested in committing suicide." Once, she said, "we had a patient who tried to commit suicide by drinking the hand sanitizer. What are we supposed to do? Can we really get rid of the hand sanitizer?"

The American College of Emergency Physicians has published several policy papers in recent years addressing the issue of psychiatric patients presenting to emergency departments in lieu of a psychiatric care facility. Dr. Mendelson said that solving the suicide problem is partly a matter of resources, and that until these problems can be solved, "the fact that there are bad things happening" is not a surprise. "We need more money, especially more federal money, to deal with this," he said.

Dr. Schneider said that her hospital is fortunate to have a psychiatric department adjacent to its emergency department, social workers who screen every patient over age 70 – older male patients are at highest risk for suicide – and a psychiatric resident available much of the time. Most hospitals "would not have a psychiatrist or psychiatric nurse on duty and would not have immediate access to a psychiatric bed," she said. "But even we will hold these patients in the ED weekends or nights," she said.

Some of the ways Dr. Schneider and her team keep patients safe in the meantime, she said, involve "colored clothes and footies" that indicate to staff and guards an at-risk patient. Staff take evaluations from the friends of young patients who might not be candid about suicidal feelings. And any input from a paramedic with concerns about the state of a patient’s home is taken seriously.

The important thing, she said, is that all members of the emergency department team are empowered to act. "In emergency medicine, we believe everyone on the team can push the button. Anyone can come to the physician or nurse and say, ‘I’m worried about the patient in room 120.’ This is a team sport."

More than a decade after issuing its first report on suicides in hospitals, the Joint Commission has followed up with a new one, reminding clinicians that suicides and suicide attempts can occur anywhere – not just in psychiatric units.

But emergency physicians say that suicides in nonpsychiatric units are part of a broader and more difficult problem to solve: a lack of appropriate care for psychiatric patients that forces other units – particularly emergency departments – to hold these patients in environments not designed for their safety.

Since 1995, the commission wrote, there have been 827 reports of patient suicides, 14% of which occurred in nonpsychiatric settings, more than half of these in emergency departments. The 827 cases represented only those voluntarily reported, the commission noted, and therefore is likely an undercount.

The suicides occurred in bathrooms, bedrooms, closets, showers, or just after patients left the hospital against medical advice. Patients hung, shot, lacerated, or asphyxiated themselves, jumped from high places, or ingested drugs. A number of suicides were carried out using materials immediately available in the hospital – bell cords, bandages, sheets, plastic bags, or elastic tubing.

Many patients who attempt suicide in hospitals are at unknown risk for suicide, and often lack a known psychiatric history, the commission noted. A number of measures that hospitals can take to become more vigilant about prevention were recommended in the report. These measures include intensifying screening of new patients, having volunteer or family "sitters" assigned to at-risk patients, improving communication during handoffs, and empowering staff to take preemptive actions.

Dr. Sandra M. Schneider, attending physician at Strong Memorial Hospital in Rochester, N.Y., and current president of the American College of Emergency Physicians, said she welcomed the Joint Commission report as a "wake-up call" to provide more intensive screening to identify at-risk patients without psychiatric histories, including people who have had a recent stroke or heart attack and who can suddenly and temporarily be vulnerable to suicidal thoughts.

However, Dr. Schneider said, better screening can solve only part of the problem. "Many hospitals are boarding or holding psychiatric patients until a bed becomes available," she said in an interview. "The bigger problem is access to timely care of these patients, and the ED is just not the best environment for them."

Dr. David J. Mendelson, an emergency physician and vice president of Medical Affairs for EmCare Inc. in Dallas, agreed. "I have nothing against the recommendations to better equip the doctors and staff to screen the patients," Dr. Mendelson said in an interview. "We do that anyway, though it’s not formalized." Nonetheless, he said, the Joint Commission findings "do not address the core problem."

Dr. Mendelson was the lead author of a 2008 survey for the American College of Emergency Physicians on the problem of psychiatric boarding, a perennial issue in EDs.

Of the survey’s 328 respondents – all ED physicians and most of them ED directors or department chairs – 79% said psychiatric patients were boarded in their EDs, with a third of the patients boarded for 6 hours or more; 62% said these patients received no psychiatric services while they were being boarded. Since 2008, Dr. Mendelson said, the problem seems to have only gotten worse, "probably because of the economy and because we’re seeing fewer patients in EDs with any sort of insurance at all."

A new nationwide survey of 603 hospital ED administrators by the Schumacher Group found that 56% of EDs are often unable to transfer mental/behavioral patients to inpatient facilities in a timely manner, and 30% are sometimes unable to do so. Only 3% reported always being able to transfer mental/behavioral patients in a timely manner. Boarding times of 12 hours or less were reported by 29% of EDs, 30% said the longest they boarded these patients was 24 hours, 20% reported waits of as long as 2 days, 11% had boarded them for up to 5 days, and 10% had boarded mental/behavioral patients for more than a week.

"The mental health problem in America is being swept under the rug for hospital emergency departments to deal with," Dr. William Schumacher, CEO of the Schumacher Group, said in a statement.

Dr. Schneider said that the process of finding a bed for a psychiatric patient can take days, and that "even though we take great precautions, the emergency department does not have a protected environment for patients who might be interested in committing suicide." Once, she said, "we had a patient who tried to commit suicide by drinking the hand sanitizer. What are we supposed to do? Can we really get rid of the hand sanitizer?"

The American College of Emergency Physicians has published several policy papers in recent years addressing the issue of psychiatric patients presenting to emergency departments in lieu of a psychiatric care facility. Dr. Mendelson said that solving the suicide problem is partly a matter of resources, and that until these problems can be solved, "the fact that there are bad things happening" is not a surprise. "We need more money, especially more federal money, to deal with this," he said.

Dr. Schneider said that her hospital is fortunate to have a psychiatric department adjacent to its emergency department, social workers who screen every patient over age 70 – older male patients are at highest risk for suicide – and a psychiatric resident available much of the time. Most hospitals "would not have a psychiatrist or psychiatric nurse on duty and would not have immediate access to a psychiatric bed," she said. "But even we will hold these patients in the ED weekends or nights," she said.

Some of the ways Dr. Schneider and her team keep patients safe in the meantime, she said, involve "colored clothes and footies" that indicate to staff and guards an at-risk patient. Staff take evaluations from the friends of young patients who might not be candid about suicidal feelings. And any input from a paramedic with concerns about the state of a patient’s home is taken seriously.

The important thing, she said, is that all members of the emergency department team are empowered to act. "In emergency medicine, we believe everyone on the team can push the button. Anyone can come to the physician or nurse and say, ‘I’m worried about the patient in room 120.’ This is a team sport."

More than a decade after issuing its first report on suicides in hospitals, the Joint Commission has followed up with a new one, reminding clinicians that suicides and suicide attempts can occur anywhere – not just in psychiatric units.

But emergency physicians say that suicides in nonpsychiatric units are part of a broader and more difficult problem to solve: a lack of appropriate care for psychiatric patients that forces other units – particularly emergency departments – to hold these patients in environments not designed for their safety.

Since 1995, the commission wrote, there have been 827 reports of patient suicides, 14% of which occurred in nonpsychiatric settings, more than half of these in emergency departments. The 827 cases represented only those voluntarily reported, the commission noted, and therefore is likely an undercount.

The suicides occurred in bathrooms, bedrooms, closets, showers, or just after patients left the hospital against medical advice. Patients hung, shot, lacerated, or asphyxiated themselves, jumped from high places, or ingested drugs. A number of suicides were carried out using materials immediately available in the hospital – bell cords, bandages, sheets, plastic bags, or elastic tubing.

Many patients who attempt suicide in hospitals are at unknown risk for suicide, and often lack a known psychiatric history, the commission noted. A number of measures that hospitals can take to become more vigilant about prevention were recommended in the report. These measures include intensifying screening of new patients, having volunteer or family "sitters" assigned to at-risk patients, improving communication during handoffs, and empowering staff to take preemptive actions.

Dr. Sandra M. Schneider, attending physician at Strong Memorial Hospital in Rochester, N.Y., and current president of the American College of Emergency Physicians, said she welcomed the Joint Commission report as a "wake-up call" to provide more intensive screening to identify at-risk patients without psychiatric histories, including people who have had a recent stroke or heart attack and who can suddenly and temporarily be vulnerable to suicidal thoughts.

However, Dr. Schneider said, better screening can solve only part of the problem. "Many hospitals are boarding or holding psychiatric patients until a bed becomes available," she said in an interview. "The bigger problem is access to timely care of these patients, and the ED is just not the best environment for them."

Dr. David J. Mendelson, an emergency physician and vice president of Medical Affairs for EmCare Inc. in Dallas, agreed. "I have nothing against the recommendations to better equip the doctors and staff to screen the patients," Dr. Mendelson said in an interview. "We do that anyway, though it’s not formalized." Nonetheless, he said, the Joint Commission findings "do not address the core problem."

Dr. Mendelson was the lead author of a 2008 survey for the American College of Emergency Physicians on the problem of psychiatric boarding, a perennial issue in EDs.

Of the survey’s 328 respondents – all ED physicians and most of them ED directors or department chairs – 79% said psychiatric patients were boarded in their EDs, with a third of the patients boarded for 6 hours or more; 62% said these patients received no psychiatric services while they were being boarded. Since 2008, Dr. Mendelson said, the problem seems to have only gotten worse, "probably because of the economy and because we’re seeing fewer patients in EDs with any sort of insurance at all."

A new nationwide survey of 603 hospital ED administrators by the Schumacher Group found that 56% of EDs are often unable to transfer mental/behavioral patients to inpatient facilities in a timely manner, and 30% are sometimes unable to do so. Only 3% reported always being able to transfer mental/behavioral patients in a timely manner. Boarding times of 12 hours or less were reported by 29% of EDs, 30% said the longest they boarded these patients was 24 hours, 20% reported waits of as long as 2 days, 11% had boarded them for up to 5 days, and 10% had boarded mental/behavioral patients for more than a week.

"The mental health problem in America is being swept under the rug for hospital emergency departments to deal with," Dr. William Schumacher, CEO of the Schumacher Group, said in a statement.

Dr. Schneider said that the process of finding a bed for a psychiatric patient can take days, and that "even though we take great precautions, the emergency department does not have a protected environment for patients who might be interested in committing suicide." Once, she said, "we had a patient who tried to commit suicide by drinking the hand sanitizer. What are we supposed to do? Can we really get rid of the hand sanitizer?"

The American College of Emergency Physicians has published several policy papers in recent years addressing the issue of psychiatric patients presenting to emergency departments in lieu of a psychiatric care facility. Dr. Mendelson said that solving the suicide problem is partly a matter of resources, and that until these problems can be solved, "the fact that there are bad things happening" is not a surprise. "We need more money, especially more federal money, to deal with this," he said.

Dr. Schneider said that her hospital is fortunate to have a psychiatric department adjacent to its emergency department, social workers who screen every patient over age 70 – older male patients are at highest risk for suicide – and a psychiatric resident available much of the time. Most hospitals "would not have a psychiatrist or psychiatric nurse on duty and would not have immediate access to a psychiatric bed," she said. "But even we will hold these patients in the ED weekends or nights," she said.

Some of the ways Dr. Schneider and her team keep patients safe in the meantime, she said, involve "colored clothes and footies" that indicate to staff and guards an at-risk patient. Staff take evaluations from the friends of young patients who might not be candid about suicidal feelings. And any input from a paramedic with concerns about the state of a patient’s home is taken seriously.

The important thing, she said, is that all members of the emergency department team are empowered to act. "In emergency medicine, we believe everyone on the team can push the button. Anyone can come to the physician or nurse and say, ‘I’m worried about the patient in room 120.’ This is a team sport."

More than a decade after issuing its first report on suicides in hospitals, the Joint Commission has followed up with a new one, reminding clinicians that suicides and suicide attempts can occur anywhere – not just in psychiatric units.

But emergency physicians say that suicides in nonpsychiatric units are part of a broader and more difficult problem to solve: a lack of appropriate care for psychiatric patients that forces other units – particularly emergency departments – to hold these patients in environments not designed for their safety.

Since 1995, the commission wrote, there have been 827 reports of patient suicides, 14% of which occurred in nonpsychiatric settings, more than half of these in emergency departments. The 827 cases represented only those voluntarily reported, the commission noted, and therefore is likely an undercount.

The suicides occurred in bathrooms, bedrooms, closets, showers, or just after patients left the hospital against medical advice. Patients hung, shot, lacerated, or asphyxiated themselves, jumped from high places, or ingested drugs. A number of suicides were carried out using materials immediately available in the hospital – bell cords, bandages, sheets, plastic bags, or elastic tubing.

Many patients who attempt suicide in hospitals are at unknown risk for suicide, and often lack a known psychiatric history, the commission noted. A number of measures that hospitals can take to become more vigilant about prevention were recommended in the report. These measures include intensifying screening of new patients, having volunteer or family "sitters" assigned to at-risk patients, improving communication during handoffs, and empowering staff to take preemptive actions.

Dr. Sandra M. Schneider, attending physician at Strong Memorial Hospital in Rochester, N.Y., and current president of the American College of Emergency Physicians, said she welcomed the Joint Commission report as a "wake-up call" to provide more intensive screening to identify at-risk patients without psychiatric histories, including people who have had a recent stroke or heart attack and who can suddenly and temporarily be vulnerable to suicidal thoughts.

However, Dr. Schneider said, better screening can solve only part of the problem. "Many hospitals are boarding or holding psychiatric patients until a bed becomes available," she said in an interview. "The bigger problem is access to timely care of these patients, and the ED is just not the best environment for them."

Dr. David J. Mendelson, an emergency physician and vice president of Medical Affairs for EmCare Inc. in Dallas, agreed. "I have nothing against the recommendations to better equip the doctors and staff to screen the patients," Dr. Mendelson said in an interview. "We do that anyway, though it’s not formalized." Nonetheless, he said, the Joint Commission findings "do not address the core problem."

Dr. Mendelson was the lead author of a 2008 survey for the American College of Emergency Physicians on the problem of psychiatric boarding, a perennial issue in EDs.

Of the survey’s 328 respondents – all ED physicians and most of them ED directors or department chairs – 79% said psychiatric patients were boarded in their EDs, with a third of the patients boarded for 6 hours or more; 62% said these patients received no psychiatric services while they were being boarded. Since 2008, Dr. Mendelson said, the problem seems to have only gotten worse, "probably because of the economy and because we’re seeing fewer patients in EDs with any sort of insurance at all."

A new nationwide survey of 603 hospital ED administrators by the Schumacher Group found that 56% of EDs are often unable to transfer mental/behavioral patients to inpatient facilities in a timely manner, and 30% are sometimes unable to do so. Only 3% reported always being able to transfer mental/behavioral patients in a timely manner. Boarding times of 12 hours or less were reported by 29% of EDs, 30% said the longest they boarded these patients was 24 hours, 20% reported waits of as long as 2 days, 11% had boarded them for up to 5 days, and 10% had boarded mental/behavioral patients for more than a week.

"The mental health problem in America is being swept under the rug for hospital emergency departments to deal with," Dr. William Schumacher, CEO of the Schumacher Group, said in a statement.

Dr. Schneider said that the process of finding a bed for a psychiatric patient can take days, and that "even though we take great precautions, the emergency department does not have a protected environment for patients who might be interested in committing suicide." Once, she said, "we had a patient who tried to commit suicide by drinking the hand sanitizer. What are we supposed to do? Can we really get rid of the hand sanitizer?"

The American College of Emergency Physicians has published several policy papers in recent years addressing the issue of psychiatric patients presenting to emergency departments in lieu of a psychiatric care facility. Dr. Mendelson said that solving the suicide problem is partly a matter of resources, and that until these problems can be solved, "the fact that there are bad things happening" is not a surprise. "We need more money, especially more federal money, to deal with this," he said.

Dr. Schneider said that her hospital is fortunate to have a psychiatric department adjacent to its emergency department, social workers who screen every patient over age 70 – older male patients are at highest risk for suicide – and a psychiatric resident available much of the time. Most hospitals "would not have a psychiatrist or psychiatric nurse on duty and would not have immediate access to a psychiatric bed," she said. "But even we will hold these patients in the ED weekends or nights," she said.

Some of the ways Dr. Schneider and her team keep patients safe in the meantime, she said, involve "colored clothes and footies" that indicate to staff and guards an at-risk patient. Staff take evaluations from the friends of young patients who might not be candid about suicidal feelings. And any input from a paramedic with concerns about the state of a patient’s home is taken seriously.

The important thing, she said, is that all members of the emergency department team are empowered to act. "In emergency medicine, we believe everyone on the team can push the button. Anyone can come to the physician or nurse and say, ‘I’m worried about the patient in room 120.’ This is a team sport."

More than a decade after issuing its first report on suicides in hospitals, the Joint Commission has followed up with a new one, reminding clinicians that suicides and suicide attempts can occur anywhere – not just in psychiatric units.

But emergency physicians say that suicides in nonpsychiatric units are part of a broader and more difficult problem to solve: a lack of appropriate care for psychiatric patients that forces other units – particularly emergency departments – to hold these patients in environments not designed for their safety.

Since 1995, the commission wrote, there have been 827 reports of patient suicides, 14% of which occurred in nonpsychiatric settings, more than half of these in emergency departments. The 827 cases represented only those voluntarily reported, the commission noted, and therefore is likely an undercount.

The suicides occurred in bathrooms, bedrooms, closets, showers, or just after patients left the hospital against medical advice. Patients hung, shot, lacerated, or asphyxiated themselves, jumped from high places, or ingested drugs. A number of suicides were carried out using materials immediately available in the hospital – bell cords, bandages, sheets, plastic bags, or elastic tubing.

Many patients who attempt suicide in hospitals are at unknown risk for suicide, and often lack a known psychiatric history, the commission noted. A number of measures that hospitals can take to become more vigilant about prevention were recommended in the report. These measures include intensifying screening of new patients, having volunteer or family "sitters" assigned to at-risk patients, improving communication during handoffs, and empowering staff to take preemptive actions.

Dr. Sandra M. Schneider, attending physician at Strong Memorial Hospital in Rochester, N.Y., and current president of the American College of Emergency Physicians, said she welcomed the Joint Commission report as a "wake-up call" to provide more intensive screening to identify at-risk patients without psychiatric histories, including people who have had a recent stroke or heart attack and who can suddenly and temporarily be vulnerable to suicidal thoughts.

However, Dr. Schneider said, better screening can solve only part of the problem. "Many hospitals are boarding or holding psychiatric patients until a bed becomes available," she said in an interview. "The bigger problem is access to timely care of these patients, and the ED is just not the best environment for them."

Dr. David J. Mendelson, an emergency physician and vice president of Medical Affairs for EmCare Inc. in Dallas, agreed. "I have nothing against the recommendations to better equip the doctors and staff to screen the patients," Dr. Mendelson said in an interview. "We do that anyway, though it’s not formalized." Nonetheless, he said, the Joint Commission findings "do not address the core problem."

Dr. Mendelson was the lead author of a 2008 survey for the American College of Emergency Physicians on the problem of psychiatric boarding, a perennial issue in EDs.

Of the survey’s 328 respondents – all ED physicians and most of them ED directors or department chairs – 79% said psychiatric patients were boarded in their EDs, with a third of the patients boarded for 6 hours or more; 62% said these patients received no psychiatric services while they were being boarded. Since 2008, Dr. Mendelson said, the problem seems to have only gotten worse, "probably because of the economy and because we’re seeing fewer patients in EDs with any sort of insurance at all."

A new nationwide survey of 603 hospital ED administrators by the Schumacher Group found that 56% of EDs are often unable to transfer mental/behavioral patients to inpatient facilities in a timely manner, and 30% are sometimes unable to do so. Only 3% reported always being able to transfer mental/behavioral patients in a timely manner. Boarding times of 12 hours or less were reported by 29% of EDs, 30% said the longest they boarded these patients was 24 hours, 20% reported waits of as long as 2 days, 11% had boarded them for up to 5 days, and 10% had boarded mental/behavioral patients for more than a week.

"The mental health problem in America is being swept under the rug for hospital emergency departments to deal with," Dr. William Schumacher, CEO of the Schumacher Group, said in a statement.

Dr. Schneider said that the process of finding a bed for a psychiatric patient can take days, and that "even though we take great precautions, the emergency department does not have a protected environment for patients who might be interested in committing suicide." Once, she said, "we had a patient who tried to commit suicide by drinking the hand sanitizer. What are we supposed to do? Can we really get rid of the hand sanitizer?"

The American College of Emergency Physicians has published several policy papers in recent years addressing the issue of psychiatric patients presenting to emergency departments in lieu of a psychiatric care facility. Dr. Mendelson said that solving the suicide problem is partly a matter of resources, and that until these problems can be solved, "the fact that there are bad things happening" is not a surprise. "We need more money, especially more federal money, to deal with this," he said.

Dr. Schneider said that her hospital is fortunate to have a psychiatric department adjacent to its emergency department, social workers who screen every patient over age 70 – older male patients are at highest risk for suicide – and a psychiatric resident available much of the time. Most hospitals "would not have a psychiatrist or psychiatric nurse on duty and would not have immediate access to a psychiatric bed," she said. "But even we will hold these patients in the ED weekends or nights," she said.

Some of the ways Dr. Schneider and her team keep patients safe in the meantime, she said, involve "colored clothes and footies" that indicate to staff and guards an at-risk patient. Staff take evaluations from the friends of young patients who might not be candid about suicidal feelings. And any input from a paramedic with concerns about the state of a patient’s home is taken seriously.

The important thing, she said, is that all members of the emergency department team are empowered to act. "In emergency medicine, we believe everyone on the team can push the button. Anyone can come to the physician or nurse and say, ‘I’m worried about the patient in room 120.’ This is a team sport."

A large population-based study has shown a link between tricyclic antidepressant medications and an increased risk of cardiovascular disease, adding to a growing body of evidence that the medications carry cardiovascular risks – both for people with and without existing disease.

In a cohort study of 14,784 adults without known CVD in Scotland, the use of tricyclic antidepressants for any amount of time and for any reason was associated with a 35% higher risk of being diagnosed with CVD within 8 years, even after accounting for potential confounders, including symptoms of anxiety and depression, which are also linked to CVD.

Tricyclic antidepressants have been shown to increase cardiac events, including myocardial infarction, in patients with CVD; however, few population-based studies have examined the effects on people without known CVD, said Mark Hamer, Ph.D., of University College London, the lead author of the findings (Eur. Heart J. (2010 Dec 11;doi:10.1093/eurheartj/ehq438). Now, "the evidence is starting to become overwhelming," Dr. Hamer said.

Tricyclic antidepressants are an older class of medication whose psychiatric use has fallen off in favor of newer agents such as selective serotonin reuptake inhibitors. However, TCAs are still used widely to treat headache, Dr. Hamer said, citing a recent meta-analysis (BMJ 2010;341:c5222) revealing tricyclics to be more effective than SSRIs and placebo in preventing migraine and tension headaches, and also to be increasingly effective with longer-term use.

For their research, Dr. Hamer and his colleagues used data from the Scottish Health Survey, an ongoing cohort study conducted every 3-5 years in Scottish households. They combined data from surveys in 1995, 1998, and 2003 in adults aged 35 years and older (age 52.4 + 11.9 years, 43.9% men) without clinically confirmed CVD. Of the total study group, 2.2%, 2.0%, and 0.7% reported taking TCAs, SSRIs, or other antidepressants (including monoamine oxidase inhibitors), respectively.

Over an average follow-up of 8 years, there were 1,434 CVD events in the study group, 26.2% of which were fatal, and 67.5% of the events were related to coronary heart disease. The risk of CVD events (including death, nonfatal myocardial infarction, coronary artery bypass, percutaneous transluminal coronary angioplasty, stroke, and heart failure) was found to be elevated in TCA users, but this was not significant after adjusting for confounding factors. No associations were found between SSRI use and CVD. Dr. Hamer and his colleagues also found no significant associations between any antidepressant use and all-cause mortality.

However, the TCA users saw a 35% higher risk of CVD (multivariate-adjusted hazard ratio 1.35, 95% confidence interval 1.03-1.77) even after adjustment for confounding factors, which included physical activity, smoking status, alcohol use, socioeconomic status, body mass index, marital status, a history of psychiatric illness, and the presence of preclinical CVD risk factors as measured by the use of cardiovascular medication and antihypertension drugs.

The investigators noted that tricyclic antidepressants have been associated with weight gain and have been shown to have cardiotoxic effects. These "might explain the increased risk of CVD, including orthostatic hypotension, reduced heart rate variability, QT interval prolongation, and greater risk of hypertension," they wrote in their analysis.

Dr. Hamer and his colleagues said that because they had shown the association between antidepressant use and CVD risk to be partly independent of psychiatric symptoms, "there may be some characteristic of TCA that is raising CVD risk." Or, they said, the risk could be explained by "residual confounding due to unmeasured or unknown risk factors."

Dr. Hamer and his colleagues wrote that the strengths of the study include its large sample size from a general population, its detailed information about hospital admissions, and the well-characterized participants, which could "facilitate insights into the role of potential confounding factors, particularly existing depression and mental illness." Among the study’s weaknesses, they acknowledged, was the inability to measure compliance to medication over time.

The Scottish Health Survey is funded by the Scottish Executive. Dr. Hamer’s and his colleagues’ research was funded in part by grant support from foundations, including the Wellcome Trust; the British Heart Foundation; the National Heart, Lung, and Blood Institute; and the National Institute on Aging. Neither Dr. Hamer nor his colleagues declared any conflicts of interest.

A large population-based study has shown a link between tricyclic antidepressant medications and an increased risk of cardiovascular disease, adding to a growing body of evidence that the medications carry cardiovascular risks – both for people with and without existing disease.

In a cohort study of 14,784 adults without known CVD in Scotland, the use of tricyclic antidepressants for any amount of time and for any reason was associated with a 35% higher risk of being diagnosed with CVD within 8 years, even after accounting for potential confounders, including symptoms of anxiety and depression, which are also linked to CVD.

Tricyclic antidepressants have been shown to increase cardiac events, including myocardial infarction, in patients with CVD; however, few population-based studies have examined the effects on people without known CVD, said Mark Hamer, Ph.D., of University College London, the lead author of the findings (Eur. Heart J. (2010 Dec 11;doi:10.1093/eurheartj/ehq438). Now, "the evidence is starting to become overwhelming," Dr. Hamer said.

Tricyclic antidepressants are an older class of medication whose psychiatric use has fallen off in favor of newer agents such as selective serotonin reuptake inhibitors. However, TCAs are still used widely to treat headache, Dr. Hamer said, citing a recent meta-analysis (BMJ 2010;341:c5222) revealing tricyclics to be more effective than SSRIs and placebo in preventing migraine and tension headaches, and also to be increasingly effective with longer-term use.

For their research, Dr. Hamer and his colleagues used data from the Scottish Health Survey, an ongoing cohort study conducted every 3-5 years in Scottish households. They combined data from surveys in 1995, 1998, and 2003 in adults aged 35 years and older (age 52.4 + 11.9 years, 43.9% men) without clinically confirmed CVD. Of the total study group, 2.2%, 2.0%, and 0.7% reported taking TCAs, SSRIs, or other antidepressants (including monoamine oxidase inhibitors), respectively.

Over an average follow-up of 8 years, there were 1,434 CVD events in the study group, 26.2% of which were fatal, and 67.5% of the events were related to coronary heart disease. The risk of CVD events (including death, nonfatal myocardial infarction, coronary artery bypass, percutaneous transluminal coronary angioplasty, stroke, and heart failure) was found to be elevated in TCA users, but this was not significant after adjusting for confounding factors. No associations were found between SSRI use and CVD. Dr. Hamer and his colleagues also found no significant associations between any antidepressant use and all-cause mortality.

However, the TCA users saw a 35% higher risk of CVD (multivariate-adjusted hazard ratio 1.35, 95% confidence interval 1.03-1.77) even after adjustment for confounding factors, which included physical activity, smoking status, alcohol use, socioeconomic status, body mass index, marital status, a history of psychiatric illness, and the presence of preclinical CVD risk factors as measured by the use of cardiovascular medication and antihypertension drugs.

The investigators noted that tricyclic antidepressants have been associated with weight gain and have been shown to have cardiotoxic effects. These "might explain the increased risk of CVD, including orthostatic hypotension, reduced heart rate variability, QT interval prolongation, and greater risk of hypertension," they wrote in their analysis.

Dr. Hamer and his colleagues said that because they had shown the association between antidepressant use and CVD risk to be partly independent of psychiatric symptoms, "there may be some characteristic of TCA that is raising CVD risk." Or, they said, the risk could be explained by "residual confounding due to unmeasured or unknown risk factors."

Dr. Hamer and his colleagues wrote that the strengths of the study include its large sample size from a general population, its detailed information about hospital admissions, and the well-characterized participants, which could "facilitate insights into the role of potential confounding factors, particularly existing depression and mental illness." Among the study’s weaknesses, they acknowledged, was the inability to measure compliance to medication over time.

The Scottish Health Survey is funded by the Scottish Executive. Dr. Hamer’s and his colleagues’ research was funded in part by grant support from foundations, including the Wellcome Trust; the British Heart Foundation; the National Heart, Lung, and Blood Institute; and the National Institute on Aging. Neither Dr. Hamer nor his colleagues declared any conflicts of interest.

A large population-based study has shown a link between tricyclic antidepressant medications and an increased risk of cardiovascular disease, adding to a growing body of evidence that the medications carry cardiovascular risks – both for people with and without existing disease.

In a cohort study of 14,784 adults without known CVD in Scotland, the use of tricyclic antidepressants for any amount of time and for any reason was associated with a 35% higher risk of being diagnosed with CVD within 8 years, even after accounting for potential confounders, including symptoms of anxiety and depression, which are also linked to CVD.

Tricyclic antidepressants have been shown to increase cardiac events, including myocardial infarction, in patients with CVD; however, few population-based studies have examined the effects on people without known CVD, said Mark Hamer, Ph.D., of University College London, the lead author of the findings (Eur. Heart J. (2010 Dec 11;doi:10.1093/eurheartj/ehq438). Now, "the evidence is starting to become overwhelming," Dr. Hamer said.

Tricyclic antidepressants are an older class of medication whose psychiatric use has fallen off in favor of newer agents such as selective serotonin reuptake inhibitors. However, TCAs are still used widely to treat headache, Dr. Hamer said, citing a recent meta-analysis (BMJ 2010;341:c5222) revealing tricyclics to be more effective than SSRIs and placebo in preventing migraine and tension headaches, and also to be increasingly effective with longer-term use.

For their research, Dr. Hamer and his colleagues used data from the Scottish Health Survey, an ongoing cohort study conducted every 3-5 years in Scottish households. They combined data from surveys in 1995, 1998, and 2003 in adults aged 35 years and older (age 52.4 + 11.9 years, 43.9% men) without clinically confirmed CVD. Of the total study group, 2.2%, 2.0%, and 0.7% reported taking TCAs, SSRIs, or other antidepressants (including monoamine oxidase inhibitors), respectively.

Over an average follow-up of 8 years, there were 1,434 CVD events in the study group, 26.2% of which were fatal, and 67.5% of the events were related to coronary heart disease. The risk of CVD events (including death, nonfatal myocardial infarction, coronary artery bypass, percutaneous transluminal coronary angioplasty, stroke, and heart failure) was found to be elevated in TCA users, but this was not significant after adjusting for confounding factors. No associations were found between SSRI use and CVD. Dr. Hamer and his colleagues also found no significant associations between any antidepressant use and all-cause mortality.

However, the TCA users saw a 35% higher risk of CVD (multivariate-adjusted hazard ratio 1.35, 95% confidence interval 1.03-1.77) even after adjustment for confounding factors, which included physical activity, smoking status, alcohol use, socioeconomic status, body mass index, marital status, a history of psychiatric illness, and the presence of preclinical CVD risk factors as measured by the use of cardiovascular medication and antihypertension drugs.

The investigators noted that tricyclic antidepressants have been associated with weight gain and have been shown to have cardiotoxic effects. These "might explain the increased risk of CVD, including orthostatic hypotension, reduced heart rate variability, QT interval prolongation, and greater risk of hypertension," they wrote in their analysis.

Dr. Hamer and his colleagues said that because they had shown the association between antidepressant use and CVD risk to be partly independent of psychiatric symptoms, "there may be some characteristic of TCA that is raising CVD risk." Or, they said, the risk could be explained by "residual confounding due to unmeasured or unknown risk factors."

Dr. Hamer and his colleagues wrote that the strengths of the study include its large sample size from a general population, its detailed information about hospital admissions, and the well-characterized participants, which could "facilitate insights into the role of potential confounding factors, particularly existing depression and mental illness." Among the study’s weaknesses, they acknowledged, was the inability to measure compliance to medication over time.

The Scottish Health Survey is funded by the Scottish Executive. Dr. Hamer’s and his colleagues’ research was funded in part by grant support from foundations, including the Wellcome Trust; the British Heart Foundation; the National Heart, Lung, and Blood Institute; and the National Institute on Aging. Neither Dr. Hamer nor his colleagues declared any conflicts of interest.