International Journal of Cardiology 221 (2016) 631
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Correspondence
Prevalence of diabetes in patients with takotsubo syndrome and controls without coronary artery disease in a Swedish cohort: Scrutiny of statistics may be enlightening John E. Madias ⁎ Icahn School of Medicine at Mount Sinai, New York, NY, United States Division of Cardiology, Elmhurst Hospital Center, Elmhurst, NY, United States
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Article history: Received 28 April 2016 Accepted 28 June 2016 Available online 5 July 2016
Keywords: Takotsubo syndrome Pathogenesis of Takotsubo syndrome Diabetes and Takotsubo syndrome Autonomic nervous system and Takotsubo syndrome Diabetic neuropathy and Takotsubo syndrome Autonomic neuropathy and Takotsubo syndrome
To the Editor, The pathogenesis of takotsubo syndrome (TTS) is still elusive. It has been reported recently that patients with TTS have a low prevalence of diabetes mellitus (DM), when compared to the general population [1,2]. It has also been hypothesized that attenuation or breakage of the brain– heart connection, stemming from DM-induced peripheral (particularly autonomic nervous system [ANS]) neuropathy [3] could be inhibitory to the emergence of TTS [1]. This may have pathogenetic implications, associating TTS more to an uninhibited overstimulation of the heart by the ANS [3], rather than to the abundance of blood-borne catecholamines [4]. In the context of the above, a recent paper [5] is of relevance. The authors observed that the “patients with TTS were characterized by a low cardiovascular risk factor profile”, they speculated about a “pathogenic role of sympathetic stimulation” for TTS, and found that the “mortality (in patients with TTS) is worse than in control subjects without coronary artery disease (CAD)” [5]. Data from the article's Table 1 reveal that statistical comparison of the prevalence of DM, between the 505 patients with TTS and the 1007 “controls” without CAD, led to a p value of 0.05 for type 1 DM, ⁎ Division of Cardiology, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373, United States. E-mail address:
[email protected].
http://dx.doi.org/10.1016/j.ijcard.2016.06.286 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
and a p value 0.32 for type 2 DM. However reanalysis of data combining the cases of type 1 and type 2 DM, i.e., 33 patients (6.5%) for patients with TTS, and 95 patients (9.4%) for the controls without CAD, leads to a p-value of 0.056, which barely fails to reach the statistically significant b0.0.5 p-value. Also if one considers, that the results of the analysis of the data in Table 1 of their article [5] may be influenced by an underlying type II error (failure to reject a false null hypothesis, i.e., it represents a “false negative” result, due to the low number of patients in the compared cohorts), and doubles the number of the patients with TTS to 1010, and the controls without CAD to 2014, keeping the same % of DM for the 2 cohorts (i.e., 6.5%, 66 patients with DM in the TTS cohort, and 9.4%, 190 patients with DM in the controls without CAD), the analysis renders a p-value of 0.007. It appears that the prevalence of DM in patients with TTS may be lower than in control subjects without CAD. What might have been useful is some more details about the DM (duration, severity, associated peripheral or ANS neuropathy) in the 33 TTS patients. Unfortunately such details are absent in patient data deriving from literature case reports, case series, and registries, equally. Another matter of significance is that the prevalence of DM in patients with TTS should be better compared with subjects from large general populations from which the cases of TTS are derived, rather than from a biased group of patients admitted with chest pain, who were found, at cardiac arteriography, not to have CAD [5]. Conflicts of interest There is nothing to disclose which could be construed as conflict of interest in connection with the submission of this manuscript. References [1] J.E. Madias, Low prevalence of diabetes mellitus in patients with Takotsubo syndrome: a plausible 'protective' effect with pathophysiologic connotations, Eur. Heart J. Acute Card. Care 5 (2016) 164–170. [2] D.L. Longo, A.S. Fauci, D.L. Kasper, et al., (Eds.), Harrison's principles of internal medicine, 18th ed.McGraw Hill Medical, New York, 2012 (pp.2042, 2968, 2969, 2984). [3] M.A. Samuels, The Brain -Heart Connection Circulation, Vol. 1162007 77–84. [4] I.S. Wittstein, D.R. Thiemann, J.A. Lima, et al., Neurohumoral features of myocardial stunning due to sudden emotional stress, N. Engl. J. Med. 352 (2005) (2005) 539–548. [5] P. Tornvall, O. Collste, E. Ehrenborg, H. Järnbert-Petterson, A case–control study of risk markers and mortality in takotsubo stress cardiomyopathy, J. Am. Coll. Cardiol. 67 (2016) 1931–1936.
