Gene Emery

NEW YORK (Reuters Health) - Ten-year results from a comparison of coronary-artery bypass grafting (CABG) with medical therapy alone has found that bypass lowers the odds of cardiovascular death by about nine percentage points in people with ischemic cardiomyopathy.

The 16% reduction in the death rate meant volunteers who received bypass grafting typically lived nearly a year and a half longer than those who received optimal nonsurgical therapy.

The findings are based on a study population of 1,212 patients with an ejection fraction of 35% or less who received bypass grafts between 2002 and 2007.

Death from any cause, the primary endpoint, occurred in 66.1% of the control patients and 58.9% of the bypass recipients (p=0.02).

When the researchers looked exclusively at cardiovascular deaths, the rates were 49.3% in the medical-therapy group and 40.5% in the group receiving bypass in addition to standard medical care (p=0.006).

The combined odds of hospitalization or death from any cause were also lower with bypass.

For death or hospitalization for cardiovascular causes, there was a 10.4 percentage point difference (p<0.001). For death or hospitalization for heart failure, the difference was 8.6 points (p<0.002). It was for 6.4 percentage points for death or hospitalization for any cause (p=0.001).

Results from the study, known as STICHES, were released April 3 at the American College of Cardiology annual scientific session in Chicago and online by the New England Journal of Medicine.

Bypass grafting "was associated with more favorable results than medical therapy alone across all clinically relevant long-term outcomes we evaluated," said the team, led by Dr. Eric Velazquez of the Duke Clinical Research Institute at Duke University, Durham, North Carolina.

The trends "resulted from a persistent and perhaps increasing effect size over time," they said. "Thus, it appears that the operative risk associated with CABG is offset by a durable effect that translates into increasing clinical benefit to at least 10 years."

Coronary artery disease kills more than 538,000 people in the United States each year. Most of the studies establishing the benefits of bypass grafting were done more than 40 years ago.

The initial version of the new study was known as STICH and it followed patients at 99 sites in 22 countries for a median of just over four and a half years. It found no significant difference between the two treatments when it came to the rate of death from any cause. However, bypass recipients were less likely to die from a cardiovascular event or to die from any cause or be hospitalized for cardiovascular causes.

STICHES extends those results to 10 years and found that any-cause death became significant.

Median survival was 7.73 years with bypass and 6.29 years without. The researchers calculated that the number needed to treat to prevent one death was 14 patients. The number needed to prevent one death from a cardiovascular cause was 11.

Other secondary measures were the rates of death combined with specific cardiovascular events. Once again, they consistently found a benefit for bypass.

There was a 15.8 percentage point difference for any cause of death or revascularization (p<0.001). For death or nonfatal myocardial infarction the difference was 6.3 points and it was for 7.2 percentage points for death or nonfatal stroke (both p=0.03).

Among the 610 people originally assigned to the bypass group, 9% did not receive a graft before the end of the trial. In the 602 assigned to medical therapy alone, 19.8% underwent bypass surgery. Eleven percent had it within the first year.

In an accompanying editorial, Drs. Robert Guyton and Andrew Smith of Emory University in Atlanta, wrote, "The STICHES 10-year results firmly extend the survival benefit of CABG in patients with advanced coronary artery disease to patients with heart failure and severe ischemic cardiomyopathy. These findings should prompt strong consideration of coronary bypass as an addition to medical therapy in shared decision making with these patients."

The National Heart Lung and Blood Institute funded this research. Two coauthors reported disclosures.

NEW YORK (Reuters Health) - Ten-year results from a comparison of coronary-artery bypass grafting (CABG) with medical therapy alone has found that bypass lowers the odds of cardiovascular death by about nine percentage points in people with ischemic cardiomyopathy.

The 16% reduction in the death rate meant volunteers who received bypass grafting typically lived nearly a year and a half longer than those who received optimal nonsurgical therapy.

The findings are based on a study population of 1,212 patients with an ejection fraction of 35% or less who received bypass grafts between 2002 and 2007.

Death from any cause, the primary endpoint, occurred in 66.1% of the control patients and 58.9% of the bypass recipients (p=0.02).

When the researchers looked exclusively at cardiovascular deaths, the rates were 49.3% in the medical-therapy group and 40.5% in the group receiving bypass in addition to standard medical care (p=0.006).

The combined odds of hospitalization or death from any cause were also lower with bypass.

For death or hospitalization for cardiovascular causes, there was a 10.4 percentage point difference (p<0.001). For death or hospitalization for heart failure, the difference was 8.6 points (p<0.002). It was for 6.4 percentage points for death or hospitalization for any cause (p=0.001).

Results from the study, known as STICHES, were released April 3 at the American College of Cardiology annual scientific session in Chicago and online by the New England Journal of Medicine.

Bypass grafting "was associated with more favorable results than medical therapy alone across all clinically relevant long-term outcomes we evaluated," said the team, led by Dr. Eric Velazquez of the Duke Clinical Research Institute at Duke University, Durham, North Carolina.

The trends "resulted from a persistent and perhaps increasing effect size over time," they said. "Thus, it appears that the operative risk associated with CABG is offset by a durable effect that translates into increasing clinical benefit to at least 10 years."

Coronary artery disease kills more than 538,000 people in the United States each year. Most of the studies establishing the benefits of bypass grafting were done more than 40 years ago.

The initial version of the new study was known as STICH and it followed patients at 99 sites in 22 countries for a median of just over four and a half years. It found no significant difference between the two treatments when it came to the rate of death from any cause. However, bypass recipients were less likely to die from a cardiovascular event or to die from any cause or be hospitalized for cardiovascular causes.

STICHES extends those results to 10 years and found that any-cause death became significant.

Median survival was 7.73 years with bypass and 6.29 years without. The researchers calculated that the number needed to treat to prevent one death was 14 patients. The number needed to prevent one death from a cardiovascular cause was 11.

Other secondary measures were the rates of death combined with specific cardiovascular events. Once again, they consistently found a benefit for bypass.

There was a 15.8 percentage point difference for any cause of death or revascularization (p<0.001). For death or nonfatal myocardial infarction the difference was 6.3 points and it was for 7.2 percentage points for death or nonfatal stroke (both p=0.03).

Among the 610 people originally assigned to the bypass group, 9% did not receive a graft before the end of the trial. In the 602 assigned to medical therapy alone, 19.8% underwent bypass surgery. Eleven percent had it within the first year.

In an accompanying editorial, Drs. Robert Guyton and Andrew Smith of Emory University in Atlanta, wrote, "The STICHES 10-year results firmly extend the survival benefit of CABG in patients with advanced coronary artery disease to patients with heart failure and severe ischemic cardiomyopathy. These findings should prompt strong consideration of coronary bypass as an addition to medical therapy in shared decision making with these patients."

The National Heart Lung and Blood Institute funded this research. Two coauthors reported disclosures.

NEW YORK (Reuters Health) - Ten-year results from a comparison of coronary-artery bypass grafting (CABG) with medical therapy alone has found that bypass lowers the odds of cardiovascular death by about nine percentage points in people with ischemic cardiomyopathy.

The 16% reduction in the death rate meant volunteers who received bypass grafting typically lived nearly a year and a half longer than those who received optimal nonsurgical therapy.

The findings are based on a study population of 1,212 patients with an ejection fraction of 35% or less who received bypass grafts between 2002 and 2007.

Death from any cause, the primary endpoint, occurred in 66.1% of the control patients and 58.9% of the bypass recipients (p=0.02).

When the researchers looked exclusively at cardiovascular deaths, the rates were 49.3% in the medical-therapy group and 40.5% in the group receiving bypass in addition to standard medical care (p=0.006).

The combined odds of hospitalization or death from any cause were also lower with bypass.

For death or hospitalization for cardiovascular causes, there was a 10.4 percentage point difference (p<0.001). For death or hospitalization for heart failure, the difference was 8.6 points (p<0.002). It was for 6.4 percentage points for death or hospitalization for any cause (p=0.001).

Results from the study, known as STICHES, were released April 3 at the American College of Cardiology annual scientific session in Chicago and online by the New England Journal of Medicine.

Bypass grafting "was associated with more favorable results than medical therapy alone across all clinically relevant long-term outcomes we evaluated," said the team, led by Dr. Eric Velazquez of the Duke Clinical Research Institute at Duke University, Durham, North Carolina.

The trends "resulted from a persistent and perhaps increasing effect size over time," they said. "Thus, it appears that the operative risk associated with CABG is offset by a durable effect that translates into increasing clinical benefit to at least 10 years."

Coronary artery disease kills more than 538,000 people in the United States each year. Most of the studies establishing the benefits of bypass grafting were done more than 40 years ago.

The initial version of the new study was known as STICH and it followed patients at 99 sites in 22 countries for a median of just over four and a half years. It found no significant difference between the two treatments when it came to the rate of death from any cause. However, bypass recipients were less likely to die from a cardiovascular event or to die from any cause or be hospitalized for cardiovascular causes.

STICHES extends those results to 10 years and found that any-cause death became significant.

Median survival was 7.73 years with bypass and 6.29 years without. The researchers calculated that the number needed to treat to prevent one death was 14 patients. The number needed to prevent one death from a cardiovascular cause was 11.

Other secondary measures were the rates of death combined with specific cardiovascular events. Once again, they consistently found a benefit for bypass.

There was a 15.8 percentage point difference for any cause of death or revascularization (p<0.001). For death or nonfatal myocardial infarction the difference was 6.3 points and it was for 7.2 percentage points for death or nonfatal stroke (both p=0.03).

Among the 610 people originally assigned to the bypass group, 9% did not receive a graft before the end of the trial. In the 602 assigned to medical therapy alone, 19.8% underwent bypass surgery. Eleven percent had it within the first year.

In an accompanying editorial, Drs. Robert Guyton and Andrew Smith of Emory University in Atlanta, wrote, "The STICHES 10-year results firmly extend the survival benefit of CABG in patients with advanced coronary artery disease to patients with heart failure and severe ischemic cardiomyopathy. These findings should prompt strong consideration of coronary bypass as an addition to medical therapy in shared decision making with these patients."

The National Heart Lung and Blood Institute funded this research. Two coauthors reported disclosures.

NEW YORK (Reuters Health) - The diabetes drug pioglitazone, given to non-diabetics with a recent history of stroke or transient ischemic attack (TIA), prevented subsequent strokes and reduced their odds of developing type 2 diabetes, a long-term multicenter study has concluded.

But the drug also increased the risk of fracture, weight gain, and edema.

After nearly five years of follow-up, the rate of stroke or heart attack was 11.8% with placebo and 9.0% with the drug (p=0.007). The target dose was 45 mg daily.

"That 25% relative reduction is a huge effect for a stroke trial," coauthor Dr. Wayne Clark, director of the Oregon Stroke Center at Oregon Health and Science University, told Reuters Health by phone. "That's on the same realm as aspirin and a big effect for stroke.

"We're always expecting negative results these days," because so many stroke drugs have failed in previous tests, he said. "This was a positive surprise."

Dr. Clark said he was particularly taken aback by the rate that diabetes developed in pioglitazone recipients. It manifested in 3.8% of drug recipients versus 7.7% of placebo

recipients (p<0.001).

"I didn't expect that at all," he said. "That has much wider implications and might take confirmatory studies."

The 3,876 volunteers studied at 179 sites worldwide were not diabetic but they had developed insulin resistance at the time of enrollment.

Drug therapy did not reduce mortality.The results of the study, known as IRIS, were presented February 17 at the American Heart Association and the American

Stroke Association's International Stroke Conference in Los Angeles, and online in the New England Journal of Medicine.

"The findings suggest that the administration of pioglitazone in 100 patients similar to those in our trial for about five years could prevent three patients from having a

stroke or myocardial infarction," the researchers wrote in the Journal. "However, during the same period, the treatment would be expected to result in bone fractures requiring surgery or hospitalization in two patients.

"It seems reasonable to consider individual treatment preference and risk of drug-related adverse events in addition to potential benefits when making patient-specific decisions regarding therapy," they concluded.

Serious fractures occurred in 5.1% of drug recipients versus 3.2% among placebo patients (p=0.003). A weight gain of more than 4.5 kg was seen in 52.2% of pioglitazone recipientscompared with 33.7% for placebo, and rates of edema were 35.6% with the drug versus 24.9% with placebo (both p<0.001).

The drug has been plagued by suspicions that it might increase the risk of heart failure and bladder cancer. In this study, 74 pioglitazone recipients developed heart failure versus 71 in the placebo group (p=0.80). A dozen drug recipients were diagnosed with bladder cancer compared with eight cases in the placebo group (p=0.37).

Dr. Clark said, "All of the stuff we're doing for risk-factor reduction -- blood pressure reduction, stop smoking and giving aspirin -- they're all on the same level of relative improvement, and all of those are widely used. Aspirin has a list of side effects that will fill up three pages."

At the start of the study, all of the volunteers were insulin resistant, at least 40 years old, and had experienced an ischemic stroke or TIA in the previous six months. Diabetics were excluded as were patients with heart failure, active liver disease, and an increased risk of bladder cancer.

By the end of the study, 60% of the pioglitazone patients were still taking their medicine compared with 67% of placebo recipients. The most common reason for discontinuing was edema or weight gain.

The National Institute of Neurological Disorders and Stroke funded this study. Eleven coauthors reported disclosures.

NEW YORK (Reuters Health) - The diabetes drug pioglitazone, given to non-diabetics with a recent history of stroke or transient ischemic attack (TIA), prevented subsequent strokes and reduced their odds of developing type 2 diabetes, a long-term multicenter study has concluded.

But the drug also increased the risk of fracture, weight gain, and edema.

After nearly five years of follow-up, the rate of stroke or heart attack was 11.8% with placebo and 9.0% with the drug (p=0.007). The target dose was 45 mg daily.

"That 25% relative reduction is a huge effect for a stroke trial," coauthor Dr. Wayne Clark, director of the Oregon Stroke Center at Oregon Health and Science University, told Reuters Health by phone. "That's on the same realm as aspirin and a big effect for stroke.

"We're always expecting negative results these days," because so many stroke drugs have failed in previous tests, he said. "This was a positive surprise."

Dr. Clark said he was particularly taken aback by the rate that diabetes developed in pioglitazone recipients. It manifested in 3.8% of drug recipients versus 7.7% of placebo

recipients (p<0.001).

"I didn't expect that at all," he said. "That has much wider implications and might take confirmatory studies."

The 3,876 volunteers studied at 179 sites worldwide were not diabetic but they had developed insulin resistance at the time of enrollment.

Drug therapy did not reduce mortality.The results of the study, known as IRIS, were presented February 17 at the American Heart Association and the American

Stroke Association's International Stroke Conference in Los Angeles, and online in the New England Journal of Medicine.

"The findings suggest that the administration of pioglitazone in 100 patients similar to those in our trial for about five years could prevent three patients from having a

stroke or myocardial infarction," the researchers wrote in the Journal. "However, during the same period, the treatment would be expected to result in bone fractures requiring surgery or hospitalization in two patients.

"It seems reasonable to consider individual treatment preference and risk of drug-related adverse events in addition to potential benefits when making patient-specific decisions regarding therapy," they concluded.

Serious fractures occurred in 5.1% of drug recipients versus 3.2% among placebo patients (p=0.003). A weight gain of more than 4.5 kg was seen in 52.2% of pioglitazone recipientscompared with 33.7% for placebo, and rates of edema were 35.6% with the drug versus 24.9% with placebo (both p<0.001).

The drug has been plagued by suspicions that it might increase the risk of heart failure and bladder cancer. In this study, 74 pioglitazone recipients developed heart failure versus 71 in the placebo group (p=0.80). A dozen drug recipients were diagnosed with bladder cancer compared with eight cases in the placebo group (p=0.37).

Dr. Clark said, "All of the stuff we're doing for risk-factor reduction -- blood pressure reduction, stop smoking and giving aspirin -- they're all on the same level of relative improvement, and all of those are widely used. Aspirin has a list of side effects that will fill up three pages."

At the start of the study, all of the volunteers were insulin resistant, at least 40 years old, and had experienced an ischemic stroke or TIA in the previous six months. Diabetics were excluded as were patients with heart failure, active liver disease, and an increased risk of bladder cancer.

By the end of the study, 60% of the pioglitazone patients were still taking their medicine compared with 67% of placebo recipients. The most common reason for discontinuing was edema or weight gain.

The National Institute of Neurological Disorders and Stroke funded this study. Eleven coauthors reported disclosures.

NEW YORK (Reuters Health) - The diabetes drug pioglitazone, given to non-diabetics with a recent history of stroke or transient ischemic attack (TIA), prevented subsequent strokes and reduced their odds of developing type 2 diabetes, a long-term multicenter study has concluded.

But the drug also increased the risk of fracture, weight gain, and edema.

After nearly five years of follow-up, the rate of stroke or heart attack was 11.8% with placebo and 9.0% with the drug (p=0.007). The target dose was 45 mg daily.

"That 25% relative reduction is a huge effect for a stroke trial," coauthor Dr. Wayne Clark, director of the Oregon Stroke Center at Oregon Health and Science University, told Reuters Health by phone. "That's on the same realm as aspirin and a big effect for stroke.

"We're always expecting negative results these days," because so many stroke drugs have failed in previous tests, he said. "This was a positive surprise."

Dr. Clark said he was particularly taken aback by the rate that diabetes developed in pioglitazone recipients. It manifested in 3.8% of drug recipients versus 7.7% of placebo

recipients (p<0.001).

"I didn't expect that at all," he said. "That has much wider implications and might take confirmatory studies."

The 3,876 volunteers studied at 179 sites worldwide were not diabetic but they had developed insulin resistance at the time of enrollment.

Drug therapy did not reduce mortality.The results of the study, known as IRIS, were presented February 17 at the American Heart Association and the American

Stroke Association's International Stroke Conference in Los Angeles, and online in the New England Journal of Medicine.

"The findings suggest that the administration of pioglitazone in 100 patients similar to those in our trial for about five years could prevent three patients from having a

stroke or myocardial infarction," the researchers wrote in the Journal. "However, during the same period, the treatment would be expected to result in bone fractures requiring surgery or hospitalization in two patients.

"It seems reasonable to consider individual treatment preference and risk of drug-related adverse events in addition to potential benefits when making patient-specific decisions regarding therapy," they concluded.

Serious fractures occurred in 5.1% of drug recipients versus 3.2% among placebo patients (p=0.003). A weight gain of more than 4.5 kg was seen in 52.2% of pioglitazone recipientscompared with 33.7% for placebo, and rates of edema were 35.6% with the drug versus 24.9% with placebo (both p<0.001).

The drug has been plagued by suspicions that it might increase the risk of heart failure and bladder cancer. In this study, 74 pioglitazone recipients developed heart failure versus 71 in the placebo group (p=0.80). A dozen drug recipients were diagnosed with bladder cancer compared with eight cases in the placebo group (p=0.37).

Dr. Clark said, "All of the stuff we're doing for risk-factor reduction -- blood pressure reduction, stop smoking and giving aspirin -- they're all on the same level of relative improvement, and all of those are widely used. Aspirin has a list of side effects that will fill up three pages."

At the start of the study, all of the volunteers were insulin resistant, at least 40 years old, and had experienced an ischemic stroke or TIA in the previous six months. Diabetics were excluded as were patients with heart failure, active liver disease, and an increased risk of bladder cancer.

By the end of the study, 60% of the pioglitazone patients were still taking their medicine compared with 67% of placebo recipients. The most common reason for discontinuing was edema or weight gain.

The National Institute of Neurological Disorders and Stroke funded this study. Eleven coauthors reported disclosures.

NEW YORK - People with type 2 diabetes are 15 percent more likely to die from any cause and 14 percent more likely to die from a cardiovascular cause than non-diabetics at any given time, according to data from several Swedish registries.

The rates are significantly lower than previous estimates. Fifteen years ago, research was suggesting that having diabetes doubled the risk of premature death.

But the new study also found that the risk was dramatically elevated among people whose type 2 diabetes appeared by age 54. The worse their glycemic control and the more evidence of renal problems, the higher the risk.

In contrast, by age 75, type 2 diabetes posed little additional risk for people with good control and no kidney issues, according to the results.

"The overall increased risk of 15 percent among type 2 diabetics in general is a very low figure that has not been found in earlier type 2 diabetes studies," coauthor Dr. Marcus Lind of Uddevalla Hospital said in a telephone interview.

"The other thing that was interesting is that when we looked at patients with good glycemic control and no renal complications, if they were 75 years age, they had a lower risk than those in the general population. That hasn't been shown before," he said.

"What we are seeing is, if you are younger, aggressive management makes a difference," said Dr. Robert Ratner, chief scientific and medical officer of the American Diabetes Association, who was not involved in the research. At age 75, "you don't have to worry about it as much."

The study, published in the October 29 New England Journal of Medicine, is the largest to date to look at premature death in general - and death from cardiovascular causes in particular - among people with type 2 diabetes.

It compared more than 435,000 diabetics who were followed for a mean of 4.6 years with more than 2 million matched controls who were tracked for a mean of 4.8 years. The diabetics had had glucose problems for an average of 5.7 years.

In terms of actual death rates, cardiovascular mortality during the study period was 7.9 percent for diabetics versus 6.1 percent for controls (adjusted hazard ratio, 1.14; 95 percent confidence interval: 1.13-1.15). The respective rates for death from any cause were 17.7 percent and 14.5 percent (aHR, 1.15; 95 percent CI: 1.14-1.16).

For patients under age 55 with glycated hemoglobin levels below 7.0 percent, the risk of death from any cause nearly doubled (aHR, 1.92; 95 percent CI: 1.75-2.11).

"Those who are younger than 55, those who have target glycemic control and no signs of any renal complications, they had a clearly-elevated risk," said Dr. Lind.

But for people over 75, the hazard was actually 5 percent lower than it was for people without diabetes (aHR, 0.95; 95 percent CI: 0.94-0.96).

When the research team factored in people with normoalbuminuria, the risks were slightly mitigated.

Heart attack was the most common cause of death among diabetics.

When glycated hemoglobin levels were at 9.7 percent and higher for people below age 55, the hazard of death from any cause more than quadrupled. The hazard of death from cardiovascular causes rose more than five-fold.

Once again, the danger was far less extreme for people over 75, the researchers found.

"Excess mortality in type 2 diabetes was substantially higher with worsening glycemic control, severe renal complications, impaired renal function, and younger age," they concluded.

Renal function is a key element, Dr. Ratner said.

The study "reinforces the importance of early aggressive management of diabetes in order to prevent premature death and the fact is that the prevention of renal disease is probably the most potent thing we can do to reduce cardiovascular events," he said.

Dr. Lind said the risk may appear lower in the elderly because older people with diabetes are more likely to be getting aggressive treatment for their high blood pressure and high lipid levels, therapy that other people who also have hypertension and high cholesterol levels might not be receiving.

"I think that's the reason the rates are a bit lower" for seniors, he said.

Dr. Ratner said he believes the data for older diabetics simply reflects the fact that "you're seeing the survival cohort. They've made it past the difficult time."

We're all going to die, he said. "The issue is when does it happen? With diabetes, it's happening years ahead of time - in their 50s and early 60s, more so than when they reach 75. The younger you are, the greater that risk. That's when aggressive therapy should be given."

NEW YORK - People with type 2 diabetes are 15 percent more likely to die from any cause and 14 percent more likely to die from a cardiovascular cause than non-diabetics at any given time, according to data from several Swedish registries.

The rates are significantly lower than previous estimates. Fifteen years ago, research was suggesting that having diabetes doubled the risk of premature death.

But the new study also found that the risk was dramatically elevated among people whose type 2 diabetes appeared by age 54. The worse their glycemic control and the more evidence of renal problems, the higher the risk.

In contrast, by age 75, type 2 diabetes posed little additional risk for people with good control and no kidney issues, according to the results.

"The overall increased risk of 15 percent among type 2 diabetics in general is a very low figure that has not been found in earlier type 2 diabetes studies," coauthor Dr. Marcus Lind of Uddevalla Hospital said in a telephone interview.

"The other thing that was interesting is that when we looked at patients with good glycemic control and no renal complications, if they were 75 years age, they had a lower risk than those in the general population. That hasn't been shown before," he said.

"What we are seeing is, if you are younger, aggressive management makes a difference," said Dr. Robert Ratner, chief scientific and medical officer of the American Diabetes Association, who was not involved in the research. At age 75, "you don't have to worry about it as much."

The study, published in the October 29 New England Journal of Medicine, is the largest to date to look at premature death in general - and death from cardiovascular causes in particular - among people with type 2 diabetes.

It compared more than 435,000 diabetics who were followed for a mean of 4.6 years with more than 2 million matched controls who were tracked for a mean of 4.8 years. The diabetics had had glucose problems for an average of 5.7 years.

In terms of actual death rates, cardiovascular mortality during the study period was 7.9 percent for diabetics versus 6.1 percent for controls (adjusted hazard ratio, 1.14; 95 percent confidence interval: 1.13-1.15). The respective rates for death from any cause were 17.7 percent and 14.5 percent (aHR, 1.15; 95 percent CI: 1.14-1.16).

For patients under age 55 with glycated hemoglobin levels below 7.0 percent, the risk of death from any cause nearly doubled (aHR, 1.92; 95 percent CI: 1.75-2.11).

"Those who are younger than 55, those who have target glycemic control and no signs of any renal complications, they had a clearly-elevated risk," said Dr. Lind.

But for people over 75, the hazard was actually 5 percent lower than it was for people without diabetes (aHR, 0.95; 95 percent CI: 0.94-0.96).

When the research team factored in people with normoalbuminuria, the risks were slightly mitigated.

Heart attack was the most common cause of death among diabetics.

When glycated hemoglobin levels were at 9.7 percent and higher for people below age 55, the hazard of death from any cause more than quadrupled. The hazard of death from cardiovascular causes rose more than five-fold.

Once again, the danger was far less extreme for people over 75, the researchers found.

"Excess mortality in type 2 diabetes was substantially higher with worsening glycemic control, severe renal complications, impaired renal function, and younger age," they concluded.

Renal function is a key element, Dr. Ratner said.

The study "reinforces the importance of early aggressive management of diabetes in order to prevent premature death and the fact is that the prevention of renal disease is probably the most potent thing we can do to reduce cardiovascular events," he said.

Dr. Lind said the risk may appear lower in the elderly because older people with diabetes are more likely to be getting aggressive treatment for their high blood pressure and high lipid levels, therapy that other people who also have hypertension and high cholesterol levels might not be receiving.

"I think that's the reason the rates are a bit lower" for seniors, he said.

Dr. Ratner said he believes the data for older diabetics simply reflects the fact that "you're seeing the survival cohort. They've made it past the difficult time."

We're all going to die, he said. "The issue is when does it happen? With diabetes, it's happening years ahead of time - in their 50s and early 60s, more so than when they reach 75. The younger you are, the greater that risk. That's when aggressive therapy should be given."

NEW YORK - People with type 2 diabetes are 15 percent more likely to die from any cause and 14 percent more likely to die from a cardiovascular cause than non-diabetics at any given time, according to data from several Swedish registries.

The rates are significantly lower than previous estimates. Fifteen years ago, research was suggesting that having diabetes doubled the risk of premature death.

But the new study also found that the risk was dramatically elevated among people whose type 2 diabetes appeared by age 54. The worse their glycemic control and the more evidence of renal problems, the higher the risk.

In contrast, by age 75, type 2 diabetes posed little additional risk for people with good control and no kidney issues, according to the results.

"The overall increased risk of 15 percent among type 2 diabetics in general is a very low figure that has not been found in earlier type 2 diabetes studies," coauthor Dr. Marcus Lind of Uddevalla Hospital said in a telephone interview.

"The other thing that was interesting is that when we looked at patients with good glycemic control and no renal complications, if they were 75 years age, they had a lower risk than those in the general population. That hasn't been shown before," he said.

"What we are seeing is, if you are younger, aggressive management makes a difference," said Dr. Robert Ratner, chief scientific and medical officer of the American Diabetes Association, who was not involved in the research. At age 75, "you don't have to worry about it as much."

The study, published in the October 29 New England Journal of Medicine, is the largest to date to look at premature death in general - and death from cardiovascular causes in particular - among people with type 2 diabetes.

It compared more than 435,000 diabetics who were followed for a mean of 4.6 years with more than 2 million matched controls who were tracked for a mean of 4.8 years. The diabetics had had glucose problems for an average of 5.7 years.

In terms of actual death rates, cardiovascular mortality during the study period was 7.9 percent for diabetics versus 6.1 percent for controls (adjusted hazard ratio, 1.14; 95 percent confidence interval: 1.13-1.15). The respective rates for death from any cause were 17.7 percent and 14.5 percent (aHR, 1.15; 95 percent CI: 1.14-1.16).

For patients under age 55 with glycated hemoglobin levels below 7.0 percent, the risk of death from any cause nearly doubled (aHR, 1.92; 95 percent CI: 1.75-2.11).

"Those who are younger than 55, those who have target glycemic control and no signs of any renal complications, they had a clearly-elevated risk," said Dr. Lind.

But for people over 75, the hazard was actually 5 percent lower than it was for people without diabetes (aHR, 0.95; 95 percent CI: 0.94-0.96).

When the research team factored in people with normoalbuminuria, the risks were slightly mitigated.

Heart attack was the most common cause of death among diabetics.

When glycated hemoglobin levels were at 9.7 percent and higher for people below age 55, the hazard of death from any cause more than quadrupled. The hazard of death from cardiovascular causes rose more than five-fold.

Once again, the danger was far less extreme for people over 75, the researchers found.

"Excess mortality in type 2 diabetes was substantially higher with worsening glycemic control, severe renal complications, impaired renal function, and younger age," they concluded.

Renal function is a key element, Dr. Ratner said.

The study "reinforces the importance of early aggressive management of diabetes in order to prevent premature death and the fact is that the prevention of renal disease is probably the most potent thing we can do to reduce cardiovascular events," he said.

Dr. Lind said the risk may appear lower in the elderly because older people with diabetes are more likely to be getting aggressive treatment for their high blood pressure and high lipid levels, therapy that other people who also have hypertension and high cholesterol levels might not be receiving.

"I think that's the reason the rates are a bit lower" for seniors, he said.

Dr. Ratner said he believes the data for older diabetics simply reflects the fact that "you're seeing the survival cohort. They've made it past the difficult time."

We're all going to die, he said. "The issue is when does it happen? With diabetes, it's happening years ahead of time - in their 50s and early 60s, more so than when they reach 75. The younger you are, the greater that risk. That's when aggressive therapy should be given."

NEW YORK - The theory that heart surgery can be made safer by periodically cutting off blood flow to an arm has been called into serious question.

Two large randomized studies, published online by the New England Journal of Medicine and presented on Oct. 5 at the European Society of Intensive Care Medicine Congress in Berlin, show that the technique, known as remote ischemic preconditioning (RIPC), made no difference in terms of the risk of death, heart attack, or kidney failure after surgery.

"The conclusions from both trials are definitive: remote ischemic preconditioning is ineffective in adults undergoing on-pump cardiac surgery," wrote Dr. Michael Zaugg and Dr. Eliana Lucchinetti of the University of Alberta in Edmonton, Canada, in a Journal editorial.

But the chief author of one of the studies, Dr. Patrick Meybohm of University Hospital Frankfurt in Germany, said research on the technique will likely continue because propofol was used as an anesthetic, which may have muted the effect, and patients who were excluded because of recent heart attack or severe liver or kidney disease might benefit.

"Other RIPC protocols (e.g., involving lower-limb RIPC, a longer duration of ischemia, or more cycles) may still be protective. Thus future studies should focus on these confounders," he said by email.

Evidence supporting the technique has been mixed, although tests that have looked at serum cardiac and renal biomarkers have suggested that cutting off flow to an extremity during on-pump surgery might offer better outcomes.

"The underlying hypothesis is that RIPC may attenuate organ injury by releasing various molecules such as damage-associated molecular patterns, adenosin, etc. etc., and that the body's own mediators may then induce natural defenses such as bioenergetic down-regulation and temporary cell-cycle arrest," Meybohm said. "These defenses, once engaged, can then protect the organs during subsequent inflammatory or ischemic stress."

The two studies, known as ERICCA and the RIPHeart, both included a sham group so the surgeons would not know which of the unconscious patients were getting their arm circulation cut off by a blood pressure cuff during the operation. Virtually all the patients were sedated with intravenous propofol.

ERICCA, the larger of the two, was conducted in the UK at 30 cardiac surgery centers on people undergoing coronary artery bypass graft surgery with or without valve replacement.

In the active treatment group, the blood was cut off from the arm for five minutes and restored for five minutes. The cycle was repeated three more times. In the control group, the inflation valve was left open.

Ultimately, 26.5% of the 801 patients in the test group died from cardiovascular causes, experienced a myocardial infarction, required coronary revascularization or experienced a stroke 12 months after randomization. The rate was 27.7% for the 811 in the control group (p=0.58).

There were no significant differences for those individual measures, nor on secondary measures such as the rate of acute kidney injury, troponin levels, length of stay in the ICU, or amount of time spent in the hospital.

The research team, led by Dr. Derek Hausenloy of University College in London, did not find any evidence that preconditioning produced serious side effects.

The RIPHeart study, conducted at 14 German hospitals by Dr. Meybohm and colleagues, randomized 1,403 patients and used a composite endpoint of death, heart attack, stroke, or acute renal failure up to the time of hospital discharge or a maximum of 14 days. A secondary analysis followed the volunteers for three months.

To disguise which patients were receiving preconditioning and which were not, cuffs were placed on each patient's arm and on a dummy arm, both covered by surgical drapes. Only one cuff was inflated.

Again, the endpoint rates in the two groups were the same - 14.3% with preconditioning and 14.6% with sham preconditioning. Analyzing the individual elements of the composite endpoint also show no advantage either way.

No significant differences were seen "in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium," the team concluded.

"In addition, no significant differences between treatment groups were found at the 30-day and 90-day follow-up," they wrote.

They also saw no adverse events. In their editorial, Drs. Zaugg and Lucchinetti speculated that the technique might be risky in patients with highly unstable coronary plaques because there was a small, albeit nonsignificant, increase in deaths from cardiovascular causes in one of the two studies.

Dr. Meybohm said he didn't think that speculation was warranted.

"Current data do not strongly support the hypothesis that RIPC may do more harm than good," he said. "There are preliminary results from about two-three studies, but there are also nearly a hundred studies demonstrating reduced biomarkers of organ ischemia/reperfusion injury, and positive/neutral effects."

The ERICCA study was funded by the Efficacy and Evaluation Program and the British Heart Foundation; the RIPHeart study was funded by the German Research Foundation.

NEW YORK - The theory that heart surgery can be made safer by periodically cutting off blood flow to an arm has been called into serious question.

Two large randomized studies, published online by the New England Journal of Medicine and presented on Oct. 5 at the European Society of Intensive Care Medicine Congress in Berlin, show that the technique, known as remote ischemic preconditioning (RIPC), made no difference in terms of the risk of death, heart attack, or kidney failure after surgery.

"The conclusions from both trials are definitive: remote ischemic preconditioning is ineffective in adults undergoing on-pump cardiac surgery," wrote Dr. Michael Zaugg and Dr. Eliana Lucchinetti of the University of Alberta in Edmonton, Canada, in a Journal editorial.

But the chief author of one of the studies, Dr. Patrick Meybohm of University Hospital Frankfurt in Germany, said research on the technique will likely continue because propofol was used as an anesthetic, which may have muted the effect, and patients who were excluded because of recent heart attack or severe liver or kidney disease might benefit.

"Other RIPC protocols (e.g., involving lower-limb RIPC, a longer duration of ischemia, or more cycles) may still be protective. Thus future studies should focus on these confounders," he said by email.

Evidence supporting the technique has been mixed, although tests that have looked at serum cardiac and renal biomarkers have suggested that cutting off flow to an extremity during on-pump surgery might offer better outcomes.

"The underlying hypothesis is that RIPC may attenuate organ injury by releasing various molecules such as damage-associated molecular patterns, adenosin, etc. etc., and that the body's own mediators may then induce natural defenses such as bioenergetic down-regulation and temporary cell-cycle arrest," Meybohm said. "These defenses, once engaged, can then protect the organs during subsequent inflammatory or ischemic stress."

The two studies, known as ERICCA and the RIPHeart, both included a sham group so the surgeons would not know which of the unconscious patients were getting their arm circulation cut off by a blood pressure cuff during the operation. Virtually all the patients were sedated with intravenous propofol.

ERICCA, the larger of the two, was conducted in the UK at 30 cardiac surgery centers on people undergoing coronary artery bypass graft surgery with or without valve replacement.

In the active treatment group, the blood was cut off from the arm for five minutes and restored for five minutes. The cycle was repeated three more times. In the control group, the inflation valve was left open.

Ultimately, 26.5% of the 801 patients in the test group died from cardiovascular causes, experienced a myocardial infarction, required coronary revascularization or experienced a stroke 12 months after randomization. The rate was 27.7% for the 811 in the control group (p=0.58).

There were no significant differences for those individual measures, nor on secondary measures such as the rate of acute kidney injury, troponin levels, length of stay in the ICU, or amount of time spent in the hospital.

The research team, led by Dr. Derek Hausenloy of University College in London, did not find any evidence that preconditioning produced serious side effects.

The RIPHeart study, conducted at 14 German hospitals by Dr. Meybohm and colleagues, randomized 1,403 patients and used a composite endpoint of death, heart attack, stroke, or acute renal failure up to the time of hospital discharge or a maximum of 14 days. A secondary analysis followed the volunteers for three months.

To disguise which patients were receiving preconditioning and which were not, cuffs were placed on each patient's arm and on a dummy arm, both covered by surgical drapes. Only one cuff was inflated.

Again, the endpoint rates in the two groups were the same - 14.3% with preconditioning and 14.6% with sham preconditioning. Analyzing the individual elements of the composite endpoint also show no advantage either way.

No significant differences were seen "in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium," the team concluded.

"In addition, no significant differences between treatment groups were found at the 30-day and 90-day follow-up," they wrote.

They also saw no adverse events. In their editorial, Drs. Zaugg and Lucchinetti speculated that the technique might be risky in patients with highly unstable coronary plaques because there was a small, albeit nonsignificant, increase in deaths from cardiovascular causes in one of the two studies.

Dr. Meybohm said he didn't think that speculation was warranted.

"Current data do not strongly support the hypothesis that RIPC may do more harm than good," he said. "There are preliminary results from about two-three studies, but there are also nearly a hundred studies demonstrating reduced biomarkers of organ ischemia/reperfusion injury, and positive/neutral effects."

The ERICCA study was funded by the Efficacy and Evaluation Program and the British Heart Foundation; the RIPHeart study was funded by the German Research Foundation.

NEW YORK - The theory that heart surgery can be made safer by periodically cutting off blood flow to an arm has been called into serious question.

Two large randomized studies, published online by the New England Journal of Medicine and presented on Oct. 5 at the European Society of Intensive Care Medicine Congress in Berlin, show that the technique, known as remote ischemic preconditioning (RIPC), made no difference in terms of the risk of death, heart attack, or kidney failure after surgery.

"The conclusions from both trials are definitive: remote ischemic preconditioning is ineffective in adults undergoing on-pump cardiac surgery," wrote Dr. Michael Zaugg and Dr. Eliana Lucchinetti of the University of Alberta in Edmonton, Canada, in a Journal editorial.

But the chief author of one of the studies, Dr. Patrick Meybohm of University Hospital Frankfurt in Germany, said research on the technique will likely continue because propofol was used as an anesthetic, which may have muted the effect, and patients who were excluded because of recent heart attack or severe liver or kidney disease might benefit.

"Other RIPC protocols (e.g., involving lower-limb RIPC, a longer duration of ischemia, or more cycles) may still be protective. Thus future studies should focus on these confounders," he said by email.

Evidence supporting the technique has been mixed, although tests that have looked at serum cardiac and renal biomarkers have suggested that cutting off flow to an extremity during on-pump surgery might offer better outcomes.

"The underlying hypothesis is that RIPC may attenuate organ injury by releasing various molecules such as damage-associated molecular patterns, adenosin, etc. etc., and that the body's own mediators may then induce natural defenses such as bioenergetic down-regulation and temporary cell-cycle arrest," Meybohm said. "These defenses, once engaged, can then protect the organs during subsequent inflammatory or ischemic stress."

The two studies, known as ERICCA and the RIPHeart, both included a sham group so the surgeons would not know which of the unconscious patients were getting their arm circulation cut off by a blood pressure cuff during the operation. Virtually all the patients were sedated with intravenous propofol.

ERICCA, the larger of the two, was conducted in the UK at 30 cardiac surgery centers on people undergoing coronary artery bypass graft surgery with or without valve replacement.

In the active treatment group, the blood was cut off from the arm for five minutes and restored for five minutes. The cycle was repeated three more times. In the control group, the inflation valve was left open.

Ultimately, 26.5% of the 801 patients in the test group died from cardiovascular causes, experienced a myocardial infarction, required coronary revascularization or experienced a stroke 12 months after randomization. The rate was 27.7% for the 811 in the control group (p=0.58).

There were no significant differences for those individual measures, nor on secondary measures such as the rate of acute kidney injury, troponin levels, length of stay in the ICU, or amount of time spent in the hospital.

The research team, led by Dr. Derek Hausenloy of University College in London, did not find any evidence that preconditioning produced serious side effects.

The RIPHeart study, conducted at 14 German hospitals by Dr. Meybohm and colleagues, randomized 1,403 patients and used a composite endpoint of death, heart attack, stroke, or acute renal failure up to the time of hospital discharge or a maximum of 14 days. A secondary analysis followed the volunteers for three months.

To disguise which patients were receiving preconditioning and which were not, cuffs were placed on each patient's arm and on a dummy arm, both covered by surgical drapes. Only one cuff was inflated.

Again, the endpoint rates in the two groups were the same - 14.3% with preconditioning and 14.6% with sham preconditioning. Analyzing the individual elements of the composite endpoint also show no advantage either way.

No significant differences were seen "in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium," the team concluded.

"In addition, no significant differences between treatment groups were found at the 30-day and 90-day follow-up," they wrote.

They also saw no adverse events. In their editorial, Drs. Zaugg and Lucchinetti speculated that the technique might be risky in patients with highly unstable coronary plaques because there was a small, albeit nonsignificant, increase in deaths from cardiovascular causes in one of the two studies.

Dr. Meybohm said he didn't think that speculation was warranted.

"Current data do not strongly support the hypothesis that RIPC may do more harm than good," he said. "There are preliminary results from about two-three studies, but there are also nearly a hundred studies demonstrating reduced biomarkers of organ ischemia/reperfusion injury, and positive/neutral effects."

The ERICCA study was funded by the Efficacy and Evaluation Program and the British Heart Foundation; the RIPHeart study was funded by the German Research Foundation.

NEW YORK — An experimental, highly sensitive troponin test cannot predict when type 2 diabetics with stable ischemic heart disease will benefit from prompt coronary revascularization, but it can show which patients are more likely to die from myocardial infarction, stroke, or other cardiovascular cases, according to a new study.

Because the troponin test measures damage to heart muscle, the outcome "suggests there's ongoing injury to patients with stable heart disease and diabetes. It has a strong association with death, heart attack, stroke, heart failure," the chief author, Dr. Brendan Everett, director of inpatient general cardiology at Brigham and Women's Hospital in Boston, told Reuters Health in a telephone interview.

But when it comes to heading off a higher risk, "we need to do more research to understand where it's coming from and what therapies might be appropriate. So it does not appear in this population that opening the coronary arteries offers any long-term benefit with respect to death or heart attack," he said.

"It tells you this is not the type of disease status that can be managed by bypass or stenting," said Dr. David Zhao, chairman of cardiology at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina. He was not involved in the research.

"From the patient's standpoint, it is disappointing," Dr. Zhao said. "But from a science standpoint, it all comes together nicely. These patients tend to have more small-vessel microvascular disease and the constant elevation of troponin indicates that there is more severe microvascular disease and more endomyocardial injury. I think it gives us the opportunity to look at more intensified medical management in this group of patients."

The study was an offshoot of the BARI 2D trial, conducted at 49 sites in six countries. It found that aggressive revascularization didn't reduce the risk of death or cardiovascular outcomes compared to intensive medical therapy alone in type 2 diabetics with stable heart disease.

In the new research, the team went back and used a highly sensitive troponin test sold in Europe but not available in the United States to see "if it could be used in stable patients to identify those who would benefit from having their coronary arteries opened with either angioplasty and stenting or bypass surgery," Dr. Everett said.

"There aren't many studies addressing that question and luckily BARI 2D had samples that were stored and available to us after the completion of the trial," he said. "What we did find was that there's clearly a group of patients that are at very high risk for death, heart attack, heart failure, and stroke."

The researchers found 27.1% of patients with a troponin T level of 14.0 ng/L or higher died from cardiovascular cause, or had a heart attack or stroke, compared to 12.9% of patients whose levels were lower, they reported online August 12 in the New England Journal of Medicine.

Adjusting for various factors, the risk of reaching one of those primary endpoints after five years was 85% greater with the higher troponin levels (P<0.001).

The risks for reaching individual components of the composite endpoint were also higher. Unadjusted five-year rates for patients with higher versus lower troponin levels were, respectively, 10.9% versus 3.5% for cardiovascular death, 18.7% versus 9.2% for myocardial infarction, 4.4% versus 2.3% for stroke, and 25.7% versus 11.1% for heart failure.

The Everett team also found that among the 897 volunteers whose levels had been at 14 or above, receiving a prompt intervention did not reduce their likelihood of reaching a primary endpoint compared to the 2,277 with normal concentrations.

The five-year rates of heart attack, stroke, or death from any cardiovascular cause were 26.5% in the revascularization group and 27.6% with medical therapy alone.

"We need to figure out how to better treat them, because fixing their coronary arteries doesn't seem to be giving them the benefit we thought it would, or hoped it would," said Dr. Everett. "For the time being, this is not a test that should be routinely used on stable patients."

The researchers also looked at how troponin levels changed over time.

"Despite aggressive medical therapy for type 2 diabetes and stable ischemic heart disease, the median troponin T concentration increased over one year of follow-up, and no significant reductions in troponin T concentrations were observed in patients who underwent coronary revascularization," the researchers said.

"If this type of patient has elevated troponin, I would be more aggressive in medical management, including statins, smoking cessation, and lifestyle changes," said Dr. Zhao of Wake Forest. "I think the next step would be to ideally run a clinical trial and see if, in patients with elevated troponin levels, intensified medical management reduces the number of events as compared to standard therapy.

NEW YORK — An experimental, highly sensitive troponin test cannot predict when type 2 diabetics with stable ischemic heart disease will benefit from prompt coronary revascularization, but it can show which patients are more likely to die from myocardial infarction, stroke, or other cardiovascular cases, according to a new study.

Because the troponin test measures damage to heart muscle, the outcome "suggests there's ongoing injury to patients with stable heart disease and diabetes. It has a strong association with death, heart attack, stroke, heart failure," the chief author, Dr. Brendan Everett, director of inpatient general cardiology at Brigham and Women's Hospital in Boston, told Reuters Health in a telephone interview.

But when it comes to heading off a higher risk, "we need to do more research to understand where it's coming from and what therapies might be appropriate. So it does not appear in this population that opening the coronary arteries offers any long-term benefit with respect to death or heart attack," he said.

"It tells you this is not the type of disease status that can be managed by bypass or stenting," said Dr. David Zhao, chairman of cardiology at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina. He was not involved in the research.

"From the patient's standpoint, it is disappointing," Dr. Zhao said. "But from a science standpoint, it all comes together nicely. These patients tend to have more small-vessel microvascular disease and the constant elevation of troponin indicates that there is more severe microvascular disease and more endomyocardial injury. I think it gives us the opportunity to look at more intensified medical management in this group of patients."

The study was an offshoot of the BARI 2D trial, conducted at 49 sites in six countries. It found that aggressive revascularization didn't reduce the risk of death or cardiovascular outcomes compared to intensive medical therapy alone in type 2 diabetics with stable heart disease.

In the new research, the team went back and used a highly sensitive troponin test sold in Europe but not available in the United States to see "if it could be used in stable patients to identify those who would benefit from having their coronary arteries opened with either angioplasty and stenting or bypass surgery," Dr. Everett said.

"There aren't many studies addressing that question and luckily BARI 2D had samples that were stored and available to us after the completion of the trial," he said. "What we did find was that there's clearly a group of patients that are at very high risk for death, heart attack, heart failure, and stroke."

The researchers found 27.1% of patients with a troponin T level of 14.0 ng/L or higher died from cardiovascular cause, or had a heart attack or stroke, compared to 12.9% of patients whose levels were lower, they reported online August 12 in the New England Journal of Medicine.

Adjusting for various factors, the risk of reaching one of those primary endpoints after five years was 85% greater with the higher troponin levels (P<0.001).

The risks for reaching individual components of the composite endpoint were also higher. Unadjusted five-year rates for patients with higher versus lower troponin levels were, respectively, 10.9% versus 3.5% for cardiovascular death, 18.7% versus 9.2% for myocardial infarction, 4.4% versus 2.3% for stroke, and 25.7% versus 11.1% for heart failure.

The Everett team also found that among the 897 volunteers whose levels had been at 14 or above, receiving a prompt intervention did not reduce their likelihood of reaching a primary endpoint compared to the 2,277 with normal concentrations.

The five-year rates of heart attack, stroke, or death from any cardiovascular cause were 26.5% in the revascularization group and 27.6% with medical therapy alone.

"We need to figure out how to better treat them, because fixing their coronary arteries doesn't seem to be giving them the benefit we thought it would, or hoped it would," said Dr. Everett. "For the time being, this is not a test that should be routinely used on stable patients."

The researchers also looked at how troponin levels changed over time.

"Despite aggressive medical therapy for type 2 diabetes and stable ischemic heart disease, the median troponin T concentration increased over one year of follow-up, and no significant reductions in troponin T concentrations were observed in patients who underwent coronary revascularization," the researchers said.

"If this type of patient has elevated troponin, I would be more aggressive in medical management, including statins, smoking cessation, and lifestyle changes," said Dr. Zhao of Wake Forest. "I think the next step would be to ideally run a clinical trial and see if, in patients with elevated troponin levels, intensified medical management reduces the number of events as compared to standard therapy.

NEW YORK — An experimental, highly sensitive troponin test cannot predict when type 2 diabetics with stable ischemic heart disease will benefit from prompt coronary revascularization, but it can show which patients are more likely to die from myocardial infarction, stroke, or other cardiovascular cases, according to a new study.

Because the troponin test measures damage to heart muscle, the outcome "suggests there's ongoing injury to patients with stable heart disease and diabetes. It has a strong association with death, heart attack, stroke, heart failure," the chief author, Dr. Brendan Everett, director of inpatient general cardiology at Brigham and Women's Hospital in Boston, told Reuters Health in a telephone interview.

But when it comes to heading off a higher risk, "we need to do more research to understand where it's coming from and what therapies might be appropriate. So it does not appear in this population that opening the coronary arteries offers any long-term benefit with respect to death or heart attack," he said.

"It tells you this is not the type of disease status that can be managed by bypass or stenting," said Dr. David Zhao, chairman of cardiology at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina. He was not involved in the research.

"From the patient's standpoint, it is disappointing," Dr. Zhao said. "But from a science standpoint, it all comes together nicely. These patients tend to have more small-vessel microvascular disease and the constant elevation of troponin indicates that there is more severe microvascular disease and more endomyocardial injury. I think it gives us the opportunity to look at more intensified medical management in this group of patients."

The study was an offshoot of the BARI 2D trial, conducted at 49 sites in six countries. It found that aggressive revascularization didn't reduce the risk of death or cardiovascular outcomes compared to intensive medical therapy alone in type 2 diabetics with stable heart disease.

In the new research, the team went back and used a highly sensitive troponin test sold in Europe but not available in the United States to see "if it could be used in stable patients to identify those who would benefit from having their coronary arteries opened with either angioplasty and stenting or bypass surgery," Dr. Everett said.

"There aren't many studies addressing that question and luckily BARI 2D had samples that were stored and available to us after the completion of the trial," he said. "What we did find was that there's clearly a group of patients that are at very high risk for death, heart attack, heart failure, and stroke."

The researchers found 27.1% of patients with a troponin T level of 14.0 ng/L or higher died from cardiovascular cause, or had a heart attack or stroke, compared to 12.9% of patients whose levels were lower, they reported online August 12 in the New England Journal of Medicine.

Adjusting for various factors, the risk of reaching one of those primary endpoints after five years was 85% greater with the higher troponin levels (P<0.001).

The risks for reaching individual components of the composite endpoint were also higher. Unadjusted five-year rates for patients with higher versus lower troponin levels were, respectively, 10.9% versus 3.5% for cardiovascular death, 18.7% versus 9.2% for myocardial infarction, 4.4% versus 2.3% for stroke, and 25.7% versus 11.1% for heart failure.

The Everett team also found that among the 897 volunteers whose levels had been at 14 or above, receiving a prompt intervention did not reduce their likelihood of reaching a primary endpoint compared to the 2,277 with normal concentrations.

The five-year rates of heart attack, stroke, or death from any cardiovascular cause were 26.5% in the revascularization group and 27.6% with medical therapy alone.

"We need to figure out how to better treat them, because fixing their coronary arteries doesn't seem to be giving them the benefit we thought it would, or hoped it would," said Dr. Everett. "For the time being, this is not a test that should be routinely used on stable patients."

The researchers also looked at how troponin levels changed over time.

"Despite aggressive medical therapy for type 2 diabetes and stable ischemic heart disease, the median troponin T concentration increased over one year of follow-up, and no significant reductions in troponin T concentrations were observed in patients who underwent coronary revascularization," the researchers said.

"If this type of patient has elevated troponin, I would be more aggressive in medical management, including statins, smoking cessation, and lifestyle changes," said Dr. Zhao of Wake Forest. "I think the next step would be to ideally run a clinical trial and see if, in patients with elevated troponin levels, intensified medical management reduces the number of events as compared to standard therapy.