Author + information
- Sergio Raposeiras-Roubín, MD⁎ (, )
- Cristina Barreiro-Pardal, MD,
- Ezequiel Álvarez, MD and
- José Ramón González Juanatey, MD, PhD
- ↵⁎Cardiology Department, Clinical University Hospital of Santiago de Compostela, Travesía Choupana s/n. 15706, Santiago de Compostela, A Coruña, Spain
We read with interest the elegantly written paper by Rubin et al. (1) relating to the analysis of the association between categories of glycated hemoglobin (HbA1c) and high-sensitivity cardiac troponin T (hs-cTnT) in participants without coronary heart disease (CHD) in the ARIC (Atherosclerosis Risk in Communities) study. In a community-based population of almost 10,000 subjects without clinically evident CHD, chronic hyperglycemia was independently associated with subclinical myocardial injury, as assessed by elevated levels of hs-cTnT in both persons with and without diabetes.
We congratulate the authors for this research. However, we have some major concerns regarding the explanation that the authors find for this relationship. In particular, although the authors already refer in the discussion that advanced glycation endproducts (AGEs) may play an important role in the association between HbA1c and hs-cTnT, we would like to emphasize this interaction. Interestingly, within the DCCT study (2), AGE levels were a better predictor of progression to complications than HbA1c, with more than one third of the variance in complications attributed to differences in AGE indices. The influence of AGE levels was even more evident in the intensive glycemic control cohort, suggesting that, although glycemic control is important, it is not sufficient to prevent progressive complications.
AGEs are molecules that appear in plasma and tissues and are generated nonenzymatically by glycation and oxidation of proteins as a consequence of the Maillard reaction, which is driven by oxidative stress in its final step. Arteriosclerosis and diastolic dysfunction are more prevalent in both diabetic patients and those with renal impairment; in this context, AGEs may provide the common pathophysiological link. An increase in AGEs can be determined fundamentally by 2 factors: the existence of chronic hyperglycemia and/or a high degree of oxidative stress (3). Although AGEs occur as a result of hyperglycemia, their effects can occur independently of glycemic control. This finding may explain the paradoxical progression of diabetic complications in some patients with comparatively good glycemic control. Results from the DCCT are consistent with the hypothesis that other factors such as oxidative stress may be more important mediators of advanced glycation than hyperglycemia per se in patients already receiving interventions directed at improving glycemic control.
We introduce the question of whether the relationship between HbA1c and hs-cTnT is primary or is mediated by AGEs. Perhaps it would be necessary to conduct a multivariate analysis to consider whether HbA1c levels predict silent coronary disease regardless of the levels of AGEs.
- American College of Cardiology Foundation
- Rubin J.,
- Matsushita K.,
- Ballantyne C.M.,
- Hoogeveen R.,
- Coresh J.,
- Selvin E.
- Yao D.,
- Brownlee M.