Cardiology Journal 2 2014-20


Authors’ response

We would like to thank Drs. Katsiki, Athyros and Karagiannis for their interest in our work [1]. The relationship of metabolic syndrome (MetS) with cardiovascular (CV) disease, dyslipidemia, hypertension, glucose intolerance, insulin resistance, overweight, obesity and type 2 diabetes mellitus is well established and widely known. In any case, it should be pinpointed that this connection is ra­ther obvious since the mentioned clinical entities are, in variable degrees of importance, part of the definition of the MetS or, alternatively, part of its predictable outcomes. It is very meritorious that the above mentioned authors have duly enlightened other aspects of the MetS, not necessarily related to the CV or endocrine systems [2]. For instance, MetS was found to be associated with increased blood lead levels [3], sex hormone binding globulin gene polymorphisms [4], augmented neck circumference [5] and heart rate turbulence [6]. Therefore, the authors’ findings are in line with our opinion that MetS is a multifactorial and polyfacetic syndrome, standing basically on 2 tightly knotted conditions: obesity and insulin resistance. While obesity causes insulin resistance, on the other hand insulin resistance modifies adipose tissue responses to insulin and thereby recapitulates the obese state [1]. This situation may be exacerbated by other concomitant factors [7, 8] like abnormalities in adipokines, vitamin D deficiency, polycystic ovary syndrome, obstructive sleep apnea, hyperuricemia, renal and hepatic diseases, as described by the authors [9–12] in their recent letter. These clinical findings are in keeping with current experimental research. It has been recently shown in animal models that insulin and its signaling cascade normally control cell growth, metabolism and survival through activation of mitogen-activated protein kinases (MAPKs) and phosphotidylinositide-3-kinase (PI3K) [13], thus suggesting an expanded and global influence of insulin on all biological systems in mammals.

Conflict of interest: none declared


  1. 1. Fisman EZ, Tenenbaum A. The metabolic syndrome entanglement: Cutting the Gordian knot. Cardiol J, 2013; 21: 1–5.
  2. 2. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. Characteristics other than the diagnostic criteria associated with metabolic syndrome: An overview. Curr Vasc Pharmacol, 2013 Apr 25. [Epub ahead of print].
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  10. 10. Athyros VG, Giouleme O, Ganotakis ES et al. Safety and impact on cardiovascular events of long-term multifactorial treatment in patients with metabolic syndrome and abnormal liver function tests: a post hoc analysis of the randomised ATTEMPT study. Arch Med Sci, 2011; 7: 796–805.
  11. 11. Athyros VG, Karagiannis A, Ganotakis ES et al.; Assessing The Treatment Effect in Metabolic syndrome without Perceptible diabeTes (ATTEMPT) Collaborative Group. Association between the changes in renal function and serum uric acid levels during multifactorial intervention and clinical outcome in patients with metabolic syndrome. A post hoc analysis of the ATTEMPT study. Curr Med Res Opin, 2011; 27: 1659–1668.
  12. 12. Athyros VG, Mikhailidis DP, Liberopoulos EN et al. Effect of statin treatment on renal function and serum uric acid levels and their relation to vascular events in patients with coronary heart disease and metabolic syndrome: A subgroup analysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. Nephrol Dial Transplant, 2007; 22: 118–127.
  13. 13. Guo S. Insulin signaling, resistance, and the metabolic syndrome: Insights from mouse models to disease mechanisms. J Endocrinol, 2014; 220: T1–T23.


Enrique Z. Fisman1, 2, Alexander Tenenbaum1, 2, 3

1Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

2Cardiovascular Diabetology Research Foundation, 5848407 Holon, Israel

tel: 972 52 7843579, e-mail:

3Cardiac Rehabilitation Institute, Sheba Medical Center, Tel-Hashomer, Israel

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