High-Sensitivity Troponin I and Outcomes in Diabetes
What is the relationship between changes in high-sensitivity cardiac troponin I (hsTnI) and cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM)?
The investigators used data from the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial, a phase IIIb clinical outcomes trial designed to evaluate the CV safety of alogliptin, a nonselective dipeptidyl peptidase 4 (DPP-4) inhibitor. Patients with T2DM, glycated hemoglobin between 6.5%-11% (or 7%-11% if they were on insulin), and a recent acute coronary syndrome (ACS) (between 15-90 days prior to randomization) were eligible for the trial. HsTnI was measured using the Abbott ARCHITECT assay at baseline and 6 months in patients randomized in the EXAMINE trial. This analysis was restricted to patients randomized ≥30 days after qualifying ACS in order to mitigate the potential for persistent hsTnI elevation following ACS (n = 3,808). The primary endpoint of the trial was CV death, myocardial infarction (MI), or stroke. CV death or heart failure was a prespecified, adjudicated secondary endpoint. A Cox proportional hazards model was used to assess the association between hsTnI and future CV events.
At baseline, hsTnI was detectable (≥1.9 ng/L) in 93% of patients and above the 99th% upper reference limit (URL) in 16%. There was a strong relationship between increasing hsTnI, both at baseline and 6 months, and the incidence of CV events through 24 months (p < 0.001 for each). Patients with undetectable hsTnI at baseline and 6 months were at the lowest risk of future CV events. Stable patients with hsTnI ≥99th% URL at 6 months were at increased risk of CV death, MI, or stroke when compared to patients with hsTnI <99th% URL irrespective of whether hsTnI was newly elevated (28.1% vs. 8.8%; adjusted hazard ratio [aHR], 2.65; 95% confidence interval [CI], 1.64-4.28; p < 0.001) or persistently so (22.5% vs. 8.8%; aHR, 1.90; 95% CI, 1.33-2.70; p < 0.001). Alogliptin neither increased nor decreased the risk of CV events compared to placebo in patients with high baseline hsTnI (22.3% vs. 23.0%; HR, 0.87; 95% CI, 0.60-1.25; p = 0.44).
The authors concluded that a substantial proportion of patients with T2DM without clinically recognized events had dynamic or persistently elevated hsTnI values and were at high risk of recurrent events.
This study reports that among patients with T2DM and established atherosclerosis, almost one in four stable patients had at least a 25% increase in hsTnI over a 6-month period. The majority had stable, rather than declining values, including among those patients with a markedly elevated baseline concentration, suggesting chronic underlying structural heart disease rather than acute myocardial injury as the etiology. It appears that serial measurements of hsTn may have a role in prevention strategies either by intensifying/prolonging therapy in patients at high risk of CV events or by developing novel therapeutic strategies. However, until studies prove that treatment based on these biomarkers actually improve patient outcomes, we should resist their use in clinical practice.
Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, ACS and Cardiac Biomarkers, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Acute Coronary Syndrome, Atherosclerosis, Biological Markers, Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Heart Failure, Hemoglobin A, Glycosylated, Insulin, Metabolic Syndrome X, Myocardial Infarction, Secondary Prevention, Standard of Care, Stroke, Troponin I, Treatment Outcome
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