Elevated troponin present in 40% with T2D and stable heart disease

CHICAGO– Abnormal levels of high-sensitivity cardiac troponin T are present in 40% of type 2 diabetic patients with stable ischemic heart disease, and they do not bode well, according to a new secondary analysis of the BARI 2D study.

In BARI 2D, an abnormal high-sensitivity cardiac troponin T (hsTnT), defined as 14 ng/L or greater, a powerful marker of ongoing myocardial injury, was independently associated with a doubled 5-year risk of the composite endpoint of cardiovascular death, MI, or stroke. Moreover, and discouragingly so, prompt coronary revascularization did nothing to mitigate that risk, Dr. Brendan M. Everett reported at the American Heart Association Scientific Sessions.

Further, early coronary revascularization did not result in a reduction in abnormal hsTnT at 1 year of follow-up, said Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.

“To better address the risk represented by an abnormal hsTnT, we need to gain an improved understanding of the biology of troponin release in this population,” he observed. “The fact that we saw an overall decrease of about 0.5% in hemoglobin A_1c and an LDL reduction of 16 mg/dL at 1 year and still there was no change in hsTnT leaves me scratching my head. The abnormal hsTnT is clearly a marker of badness, but where is it coming from? Can we address it? Or are we just left to look at it and worry about our patients who have an abnormal hsTnT?”

The BARI 2D trial was designed to learn whether patients with type 2 diabetes and stable ischemic heart disease benefit from prompt coronary revascularization plus intensive medical therapy as compared with intensive medical therapy alone. As previously reported (N. Engl. J. Med. 2009;360:2503-15), this proved not to be the case; prompt revascularization conferred no outcome advantage.

The aim of Dr. Everett’s new secondary analysis of BARI 2D was to learn if the hsTnT assay can be used to identify a subgroup of patients with type 2 diabetes and stable ischemic heart disease who might benefit from prompt coronary revascularization. The rationale was that, in patients with acute coronary syndromes, it’s well established that an abnormal hsTnT is associated with poor prognosis, and such patients would benefit from early revascularization.

The secondary analysis included 2,285 type 2 diabetics with stable ischemic heart disease whose physicians first decided whether they were better candidates for percutaneous coronary intervention or CABG surgery. Patients were then randomized to prompt revascularization by the preferred method plus intensive medical therapy or to intensive medical therapy alone.

Forty percent of participants had an abnormal hsTnT at baseline. Their 5-year rate of the composite primary endpoint of cardiovascular death, MI, or stroke was 27.1%, compared with 12.9% in patients with a baseline hsTnT below 14 ng/mL. After adjusting in a multivariate analysis for various potential confounders – including age, race, and the standard cardiovascular risk factors – the group with an abnormal baseline hsTnT had a 2.09-fold increased risk of a major cardiovascular event.

Early revascularization, regardless of whether by percutaneous coronary intervention or coronary artery bypass graft surgery, provided no benefit no matter what the patient’s baseline hsTnT level. In patients with an hsTnT of 14 ng/L or greater, the 5-year rate of the composite outcome was 26.5% with early revascularization compared with 27.6% with intensive medical therapy. In those with an hsTnT below 14 ng/L, the rate was 11.8% in the early revascularization group and 14% with medical management, a trend favoring prompt revascularization that didn’t achieve statistical significance, according to Dr. Everett.

Of patients with an abnormal hsTnT at baseline, 77% still had an abnormal value at 1 year, regardless of whether they underwent prompt revascularization or intensive medical therapy alone.

Session moderator Dr. Mikhail N. Kosiborod commented that the new BARI 2D substudy highlights a dilemma: “We know that a large population of patients with diabetes, and to some extent those with prediabetes, have elevated hsTnT levels, and we know those patients don’t do well. What we don’t know is what to do about it.”

“What [Dr. Everett’s] study clearly demonstrates is that this does not appear to be driven by epicardial coronary artery disease. If we fix the epicardial CAD, it has absolutely no impact on the outcomes nor on the actual troponin level at follow-up. As far as I can tell, it doesn’t appear to be a glycemic control issue, either. It appears that this is a humoral issue. There are ‘evil humors’ – whatever they are – and we don’t really understand what they are or what to do about it,” said Dr. Kosiborod, professor of medicine at the University of Missouri, Kansas City.

“The truth of the matter is we have no idea what’s causing this low-grade myocardial necrosis, and it’s a hugely important thing,” he continued. “There is absolutely no question that elevated hsTnT, even at very low levels, has a huge impact on subsequent risk of heart failure. We know what the public health effects of heart failure are. And patients with diabetes and heart failure tend to do particularly poorly.”

The BARI 2D trial was funded by the National Institutes of Health. Dr. Everett’s secondary analysis was funded by Roche Diagnostics. He reported receiving research grants from Roche and Novartis.

bjancin@frontlinemedcom.com

CHICAGO– Abnormal levels of high-sensitivity cardiac troponin T are present in 40% of type 2 diabetic patients with stable ischemic heart disease, and they do not bode well, according to a new secondary analysis of the BARI 2D study.

In BARI 2D, an abnormal high-sensitivity cardiac troponin T (hsTnT), defined as 14 ng/L or greater, a powerful marker of ongoing myocardial injury, was independently associated with a doubled 5-year risk of the composite endpoint of cardiovascular death, MI, or stroke. Moreover, and discouragingly so, prompt coronary revascularization did nothing to mitigate that risk, Dr. Brendan M. Everett reported at the American Heart Association Scientific Sessions.

Further, early coronary revascularization did not result in a reduction in abnormal hsTnT at 1 year of follow-up, said Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.

“To better address the risk represented by an abnormal hsTnT, we need to gain an improved understanding of the biology of troponin release in this population,” he observed. “The fact that we saw an overall decrease of about 0.5% in hemoglobin A_1c and an LDL reduction of 16 mg/dL at 1 year and still there was no change in hsTnT leaves me scratching my head. The abnormal hsTnT is clearly a marker of badness, but where is it coming from? Can we address it? Or are we just left to look at it and worry about our patients who have an abnormal hsTnT?”

The BARI 2D trial was designed to learn whether patients with type 2 diabetes and stable ischemic heart disease benefit from prompt coronary revascularization plus intensive medical therapy as compared with intensive medical therapy alone. As previously reported (N. Engl. J. Med. 2009;360:2503-15), this proved not to be the case; prompt revascularization conferred no outcome advantage.

The aim of Dr. Everett’s new secondary analysis of BARI 2D was to learn if the hsTnT assay can be used to identify a subgroup of patients with type 2 diabetes and stable ischemic heart disease who might benefit from prompt coronary revascularization. The rationale was that, in patients with acute coronary syndromes, it’s well established that an abnormal hsTnT is associated with poor prognosis, and such patients would benefit from early revascularization.

The secondary analysis included 2,285 type 2 diabetics with stable ischemic heart disease whose physicians first decided whether they were better candidates for percutaneous coronary intervention or CABG surgery. Patients were then randomized to prompt revascularization by the preferred method plus intensive medical therapy or to intensive medical therapy alone.

Forty percent of participants had an abnormal hsTnT at baseline. Their 5-year rate of the composite primary endpoint of cardiovascular death, MI, or stroke was 27.1%, compared with 12.9% in patients with a baseline hsTnT below 14 ng/mL. After adjusting in a multivariate analysis for various potential confounders – including age, race, and the standard cardiovascular risk factors – the group with an abnormal baseline hsTnT had a 2.09-fold increased risk of a major cardiovascular event.

Early revascularization, regardless of whether by percutaneous coronary intervention or coronary artery bypass graft surgery, provided no benefit no matter what the patient’s baseline hsTnT level. In patients with an hsTnT of 14 ng/L or greater, the 5-year rate of the composite outcome was 26.5% with early revascularization compared with 27.6% with intensive medical therapy. In those with an hsTnT below 14 ng/L, the rate was 11.8% in the early revascularization group and 14% with medical management, a trend favoring prompt revascularization that didn’t achieve statistical significance, according to Dr. Everett.

Of patients with an abnormal hsTnT at baseline, 77% still had an abnormal value at 1 year, regardless of whether they underwent prompt revascularization or intensive medical therapy alone.

Session moderator Dr. Mikhail N. Kosiborod commented that the new BARI 2D substudy highlights a dilemma: “We know that a large population of patients with diabetes, and to some extent those with prediabetes, have elevated hsTnT levels, and we know those patients don’t do well. What we don’t know is what to do about it.”

“What [Dr. Everett’s] study clearly demonstrates is that this does not appear to be driven by epicardial coronary artery disease. If we fix the epicardial CAD, it has absolutely no impact on the outcomes nor on the actual troponin level at follow-up. As far as I can tell, it doesn’t appear to be a glycemic control issue, either. It appears that this is a humoral issue. There are ‘evil humors’ – whatever they are – and we don’t really understand what they are or what to do about it,” said Dr. Kosiborod, professor of medicine at the University of Missouri, Kansas City.

“The truth of the matter is we have no idea what’s causing this low-grade myocardial necrosis, and it’s a hugely important thing,” he continued. “There is absolutely no question that elevated hsTnT, even at very low levels, has a huge impact on subsequent risk of heart failure. We know what the public health effects of heart failure are. And patients with diabetes and heart failure tend to do particularly poorly.”

The BARI 2D trial was funded by the National Institutes of Health. Dr. Everett’s secondary analysis was funded by Roche Diagnostics. He reported receiving research grants from Roche and Novartis.

bjancin@frontlinemedcom.com

CHICAGO– Abnormal levels of high-sensitivity cardiac troponin T are present in 40% of type 2 diabetic patients with stable ischemic heart disease, and they do not bode well, according to a new secondary analysis of the BARI 2D study.

In BARI 2D, an abnormal high-sensitivity cardiac troponin T (hsTnT), defined as 14 ng/L or greater, a powerful marker of ongoing myocardial injury, was independently associated with a doubled 5-year risk of the composite endpoint of cardiovascular death, MI, or stroke. Moreover, and discouragingly so, prompt coronary revascularization did nothing to mitigate that risk, Dr. Brendan M. Everett reported at the American Heart Association Scientific Sessions.

Further, early coronary revascularization did not result in a reduction in abnormal hsTnT at 1 year of follow-up, said Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.

“To better address the risk represented by an abnormal hsTnT, we need to gain an improved understanding of the biology of troponin release in this population,” he observed. “The fact that we saw an overall decrease of about 0.5% in hemoglobin A_1c and an LDL reduction of 16 mg/dL at 1 year and still there was no change in hsTnT leaves me scratching my head. The abnormal hsTnT is clearly a marker of badness, but where is it coming from? Can we address it? Or are we just left to look at it and worry about our patients who have an abnormal hsTnT?”

The BARI 2D trial was designed to learn whether patients with type 2 diabetes and stable ischemic heart disease benefit from prompt coronary revascularization plus intensive medical therapy as compared with intensive medical therapy alone. As previously reported (N. Engl. J. Med. 2009;360:2503-15), this proved not to be the case; prompt revascularization conferred no outcome advantage.

The aim of Dr. Everett’s new secondary analysis of BARI 2D was to learn if the hsTnT assay can be used to identify a subgroup of patients with type 2 diabetes and stable ischemic heart disease who might benefit from prompt coronary revascularization. The rationale was that, in patients with acute coronary syndromes, it’s well established that an abnormal hsTnT is associated with poor prognosis, and such patients would benefit from early revascularization.

The secondary analysis included 2,285 type 2 diabetics with stable ischemic heart disease whose physicians first decided whether they were better candidates for percutaneous coronary intervention or CABG surgery. Patients were then randomized to prompt revascularization by the preferred method plus intensive medical therapy or to intensive medical therapy alone.

Forty percent of participants had an abnormal hsTnT at baseline. Their 5-year rate of the composite primary endpoint of cardiovascular death, MI, or stroke was 27.1%, compared with 12.9% in patients with a baseline hsTnT below 14 ng/mL. After adjusting in a multivariate analysis for various potential confounders – including age, race, and the standard cardiovascular risk factors – the group with an abnormal baseline hsTnT had a 2.09-fold increased risk of a major cardiovascular event.

Early revascularization, regardless of whether by percutaneous coronary intervention or coronary artery bypass graft surgery, provided no benefit no matter what the patient’s baseline hsTnT level. In patients with an hsTnT of 14 ng/L or greater, the 5-year rate of the composite outcome was 26.5% with early revascularization compared with 27.6% with intensive medical therapy. In those with an hsTnT below 14 ng/L, the rate was 11.8% in the early revascularization group and 14% with medical management, a trend favoring prompt revascularization that didn’t achieve statistical significance, according to Dr. Everett.

Of patients with an abnormal hsTnT at baseline, 77% still had an abnormal value at 1 year, regardless of whether they underwent prompt revascularization or intensive medical therapy alone.

Session moderator Dr. Mikhail N. Kosiborod commented that the new BARI 2D substudy highlights a dilemma: “We know that a large population of patients with diabetes, and to some extent those with prediabetes, have elevated hsTnT levels, and we know those patients don’t do well. What we don’t know is what to do about it.”

“What [Dr. Everett’s] study clearly demonstrates is that this does not appear to be driven by epicardial coronary artery disease. If we fix the epicardial CAD, it has absolutely no impact on the outcomes nor on the actual troponin level at follow-up. As far as I can tell, it doesn’t appear to be a glycemic control issue, either. It appears that this is a humoral issue. There are ‘evil humors’ – whatever they are – and we don’t really understand what they are or what to do about it,” said Dr. Kosiborod, professor of medicine at the University of Missouri, Kansas City.

“The truth of the matter is we have no idea what’s causing this low-grade myocardial necrosis, and it’s a hugely important thing,” he continued. “There is absolutely no question that elevated hsTnT, even at very low levels, has a huge impact on subsequent risk of heart failure. We know what the public health effects of heart failure are. And patients with diabetes and heart failure tend to do particularly poorly.”

The BARI 2D trial was funded by the National Institutes of Health. Dr. Everett’s secondary analysis was funded by Roche Diagnostics. He reported receiving research grants from Roche and Novartis.

bjancin@frontlinemedcom.com