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Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3359 (Published 05 September 2018) Cite this as: BMJ 2018;362:k3359

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Primary prevention with statins for older adults

Pleiotropic effects of statins are more pronounced in conditions of chronic hyperglycemia?

In a retrospective cohort study of patients aged 75 or more, Ramos and colleagues found reduction in CVD in those without diabetes using statin treatment for primary prevention. In the presence of diabetes, statin use was associated with reductions in the incidence of CVD and in total mortality [1]. The fact that the effect of statin treatment in the primary prevention in the older population varies depending on the presence of type 2 diabetes seems to us very interesting in connection with the results of the ACCORD study. This RCT study showed that aggressive blood glucose control in patients with type 2 diabetes can increase mortality, including death from CVD [2]. The reason for this unexpected finding is still unknown. Many years the main doctrine has been that insulin resistance is the only pathological characteristic. However, in response to overfeeding skeletal and cardiac muscle develops insulin resistance, which promotes diversion of excess nutrients to adipose tissue for safe storage. Therefore some authors have proposed that this induction of insulin resistance protects important tissues from nutrient-induced dysfunction [3]. For example, we were able to show that the lowest total and CVD mortality in type 2 diabetes patients is associated with overweight or even light obesity [4]. The decrease in GLUT4 and caveolin-1 associated with statins treatment results in decreased glucose uptake and increased insulin resistance in adipose tissue as well as in muscle and liver, which may leads to hyperglycemia and hyperinsulinemia, early markers of type 2 diabetes [5]. Possible explanations for the so-called "reverse epidemiology" in the context of chronic heart failure are presented back in 2004 [2] and include not only the category of "reverse causation".
It can be assumed that non-lipid-related (pleiotropic) effects of statins are more pronounced in conditions of chronic hyperglycemia.
Reference
1. Ramos R, Comas-Cufí M, Martí-Lluch R, etal . Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ 2018;362:k3359.
2. Gerstein, H.C., Miller, M.E., Genuth, S., Ismail-Beigi, F., Buse, J.B., Goff, J.D., Probstfield, J.L., Cushman, W.C., Ginsberg, H.N., Bigger, J.T. and Grimm, J.R., 2011. Long-term effects of intensive glucose lowering on cardiovascular outcomes. The New England journal of medicine, 364(9), pp.818-828.
3. Nolan, C.J., Ruderman, N.B., Kahn, S.E., Pedersen, O. and Prentki, M., 2015. Insulin resistance as a physiological defense against metabolic stress: implications for the management of subsets of type 2 diabetes. Diabetes, 64(3), pp.673-686.
4. Khalangot, M., Tronko, M., Kravchenko, V., Kulchinska, J. and Hu, G., 2008. Body mass index and the risk of total and cardiovascular mortality among patients with type 2 diabetes: a large prospective study in Ukraine. Heart. doi:10.1136/hrt.2008.150524
5. Brault, M., Ray, J., Gomez, Y.H., Mantzoros, C.S. and Daskalopoulou, S.S., 2014. Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metabolism, 63(6), pp.735-745.
6. Kalantar-Zadeh, K., Block, G., Horwich, T., & Fonarow, G. C. (2004). Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. Journal of the American College of Cardiology, 43(8), 1439-1444.

Competing interests: No competing interests

15 September 2018
Mykola Khalangot
MD (Endocrinology)
SHUPYK NATIONAL MEDICAL ACADEMY OF POSTGRADUATE EDUCATION
Dorohozhytska 9 Kyiv 04112 Ukraine