High Troponin T Foretells Poor Outcomes in Patients With Type 2 Diabetes, Stable Heart Disease


In patients with type 2 diabetes and stable ischemic heart disease, abnormally high cardiac troponin T levels are common and predict an increased risk of adverse outcomes, according to an ancillary study of the BARI 2D trial published in the August 13, 2015, issue of the New England Journal of Medicine. These high-risk patients do not, however, derive a benefit from prompt revascularization compared with intensive medical therapy.

Take Home: High Troponin T Foretells Poor Outcomes in Patients With Type 2 Diabetes, Stable Heart Disease

“These results, when viewed in the context of other trials involving patients with chronic stable angina, emphasize the importance of taking a detailed history in distinguishing stable from unstable coronary heart disease and support initial medical therapy as a reasonable first approach in patients who do not have unstable [CAD],” Brendan M. Everett, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), and colleagues write.

BARI 2D enrolled patients with type 2 diabetes and stable ischemic heart disease with mild or no symptoms of angina who were candidates for CABG or PCI, randomizing them to prompt revascularization plus intensive medical therapy or medical therapy alone. The main results showed that the rate of cardiovascular death, MI, or stroke (primary composite endpoint) did not differ between the groups at 5 years.

The new analysis includes the 2,285 patients who had troponin T levels successfully measured at baseline using a high-sensitivity electrochemiluminescence assay. Nearly all patients (99.6%) had detectable troponin (≥ 3 ng/L), and 39.3% had abnormal levels (≥ 14 ng/L). Median troponin level did not differ between the revascularization and control groups (11.7 vs 11.6 ng/L; P = .41). 

High Levels Linked to 5-Year Risk

Through 5 years of follow-up, patients with abnormal troponin levels at baseline had higher rates of the primary composite endpoint and several secondary outcomes. The differences remained after adjustment for cardiovascular risk factors, history of MI, history of heart failure, severity of diabetes, renal function, electrocardiographic abnormalities, the proportion of myocardium supplied by diseased coronary arteries, number of coronary lesions, and abnormal ejection fraction (table 1).

Table 1. Outcomes at 5 Years by Baseline Troponin T Level


Further adjustment for log-transformed NT-proBNP attenuated the risk of adverse events for patients with high troponin T, although the relationships were still significant.

Among those with abnormal troponin levels at baseline, prompt revascularization was not associated with a reduction in the primary composite endpoint (HR 0.96; 95% CI 0.74-1.25), with similar findings in the overall cohort and in those with normal troponin levels at baseline.

In an analysis of patients who had troponin measures at both time points, there was a small increase in troponin between baseline and 1 year (median 3.4%; P < .001), with no difference between the revascularization and control arms.

Most patients (86.4%) had troponin T levels that increased or decreased by 25% or less between baseline and 1 year, while 6.7% and 6.9% of patients saw greater than 25% increases and decreases, respectively. Compared with troponin variations of 25% or less in the first year, abnormal baseline troponin T (HR 1.71; 95% CI 1.28-2.27) and an increase greater than 25% (HR 1.82; 95% CI 1.18-2.80) independently predicted a greater risk of the primary composite endpoint.

Troponin T a ‘Powerful Prognostic Marker’

Prior research has shown that cardiac troponin levels are associated with prognosis in ACS patients and identify patients likely to benefit from an early invasive strategy, according to the authors. 

Now, the findings of this study suggest “that high-sensitivity cardiac troponin T concentration is a powerful prognostic marker in patients who have both type 2 diabetes and stable ischemic heart disease,” they write, noting that all patients were receiving intensive medical therapy that resulted in clinically significant reductions in blood pressure, triglycerides, and glycated hemoglobin. 

The lack of benefit seen with prompt revascularization contrasts with findings in the ACS population, they say, pointing out that “the circulating concentrations of cardiac troponin T observed in the BARI 2D trial, however, were much lower than those that are seen in patients with [ACS].”

In an accompanying editorial, Chiara Melloni, MD, MHS, and Matthew T. Roe, MD, MHS, of the Duke Clinical Research Institute (Durham, NC), write that the findings have implications for the management of stable ischemic heart disease and the future evaluation of treatments. 

First, they say, more research is needed to determine whether the thresholds for determining definite myocardial necrosis with high-sensitivity troponin assays are comparable in patients with suspected ACS and those with stable disease. 

Second, elevated troponin levels might be considered as “a factor that is used to specify inclusion criteria for clinical trials to enhance event rates in a randomized population,” they continue. 

Third, “pathophysiological mechanisms that may contribute to elevated troponin values in patients with stable ischemic heart disease need to be investigated with the use of cardiovascular imaging studies, such as cardiac magnetic resonance imaging or atherosclerotic plaque imaging techniques, as well as with the use of biomarkers that reflect platelet and coagulation system activity,” they write. 

And lastly, Drs. Melloni and Roe say, future studies should assess whether patients with stable disease and elevated troponin levels will benefit more from recommended therapies, like antiplatelet drugs and statins.

 


Sources: 
1. Everett BM, Brooks MM, Vlachos HEA, et al. Troponin and cardiac events in stable ischemic heart disease and diabetes. N Engl J Med. 2015;373:610-620.
2. Melloni C, Roe MT. Cardiac troponin and risk stratification in ischemic heart disease [editorial]. N Engl J Med. 2015;373:672-674.

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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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Disclosures
  • The study was supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases and by an investigator-initiated research grant from Roche Diagnostics.
  • Dr. Everett reports receiving grant support from Novartis and Roche and fees from Genzyme for serving on a clinical events committee.
  • Dr. Roe reports receiving grant support from Daiichi Sankyo, Eli Lilly, the Familial Hypercholesterolemia Foundation, Ferring Pharmaceuticals, Janssen, KAI Pharmaceuticals, and Sanofi-Aventis and personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Elsevier Publishers, Janssen, Merck, PriMed, and Regeneron.
  • Dr. Melloni reports no relevant conflicts of interest.

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