Abstract
Type 2 diabetes mellitus (T2DM) is a rapidly evolving global health issue associated with a markedly increased risk of cardiovascular (CV) morbidity and mortality. The hyperglycaemic milieu contributes to the development of CV complications via several pathological pathways, leading to increased arterial stiffness (AS), that can be considered as a predictor of CV events in patients with diabetes. The measurement of AS is increasingly used for the clinical assessment of patients. Several methodologies were used in extensive population studies to assess AS; the most commonly used is the pulse wave velocity (PWV). The cardio-ankle vascular index (CAVI) was developed to measure AS; it is not affected by blood pressure at the time of measurement and shows stable values in healthy persons for years. There are several potential pharmacological and non-pharmacological interventions aiming to reduce AS. Recent evidence from clinical trials suggests that newer antidiabetic drugs do not only exert glycaemic-lowering properties but also decrease CV risk. In this context, sodium glucose cotransporter- 2 inhibitors (SGLT2i) ( empagliflozin, canagliflozin and dapagliflozin) significantly reduced the risk of CV and all-cause mortality (only EMPA-REG OUTCOME study) and hospitalization for heart failure in patients with T2DM with established CV disease and/or with CV risk factors. Improved endothelial function and AS probably represents one of the mechanisms by which these drugs exert their beneficial effects. The present review aimed both to describe the association between AS and T2DM and to discuss the effectiveness of SGLT2i on vascular endothelial dysfunction and AS.
Keywords: Arterial stiffness, canagliflozin, cardiovascular disease, dapagliflozin, diabetes mellitus, empagliflozin, sodium glucose cotransporter.
Graphical Abstract
[http://dx.doi.org/10.1093/ndt/gfq614] [PMID: 20947536]
[http://dx.doi.org/10.1152/ajpheart.00087.2018] [PMID: 29631368]
[http://dx.doi.org/10.1093/ndt/gft309] [PMID: 24084326]
[http://dx.doi.org/10.1373/clinchem.2018.287623] [PMID: 30459170]
[http://dx.doi.org/10.1016/j.cjca.2016.02.070] [PMID: 27118293]
[http://dx.doi.org/10.1161/hc1002.105135] [PMID: 11889014]
[http://dx.doi.org/10.2337/dc16-1773]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05494] [PMID: 26056335]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.105445] [PMID: 18426997]
[http://dx.doi.org/10.1152/ajpheart.00040.2010] [PMID: 20435849]
[http://dx.doi.org/10.1159/000096746] [PMID: 17075214]
[http://dx.doi.org/10.1161/01.HYP.38.3.429] [PMID: 11566917]
[http://dx.doi.org/10.1080/10641963.2019.1590385] [PMID: 30964359]
[http://dx.doi.org/10.5507/bp.2017.028] [PMID: 28627523]
[http://dx.doi.org/10.2337/diacare.14.12.1132] [PMID: 1773700]
[http://dx.doi.org/10.1016/S0952-3278(99)80022-2] [PMID: 10471131]
[http://dx.doi.org/10.1093/ehjci/jev332] [PMID: 26758407]
[http://dx.doi.org/10.1161/JAHA.117.005974] [PMID: 28784651]
[http://dx.doi.org/10.1007/s001250051249] [PMID: 10491751]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.144725] [PMID: 20083729]
[http://dx.doi.org/10.1016/S0140-6736(10)60484-9] [PMID: 20609967]
[http://dx.doi.org/10.1093/eurheartj/ehl254] [PMID: 17000623]
[http://dx.doi.org/10.1177/1932296816636894] [PMID: 26956240]
[http://dx.doi.org/10.2337/dc12-1463] [PMID: 23610081]
[http://dx.doi.org/10.1161/01.HYP.0000111829.46090.92] [PMID: 14698999]
[http://dx.doi.org/10.1001/jama.1990.03440210043030] [PMID: 2338751]
[http://dx.doi.org/10.1007/s00125-007-0918-3] [PMID: 18239908]
[http://dx.doi.org/10.1097/00004872-200301000-00002] [PMID: 12544424]
[PMID: 19436651]
[http://dx.doi.org/10.1159/000096744] [PMID: 17075212]
[http://dx.doi.org/10.1210/jc.2005-2559] [PMID: 16926247]
[http://dx.doi.org/10.1210/jc.2015-4069] [PMID: 26885882]
[http://dx.doi.org/10.1111/j.1755-5922.2010.00177.x] [PMID: 20626403]
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.12.023] [PMID: 25558032]
[http://dx.doi.org/10.1016/S0735-1097(01)01746-6] [PMID: 11788217]
[http://dx.doi.org/10.1093/eurheartj/ehz350] [PMID: 31211361]
[http://dx.doi.org/10.1016/j.echo.2007.11.011] [PMID: 18261694]
[http://dx.doi.org/10.1001/jama.2012.9630] [PMID: 22910757]
[http://dx.doi.org/10.1007/s12265-012-9359-6] [PMID: 22447229]
[http://dx.doi.org/10.1161/01.CIR.0000091257.27563.32] [PMID: 14504252]
[http://dx.doi.org/10.1097/00004872-200403000-00013] [PMID: 15076156]
[http://dx.doi.org/10.1097/HJH.0b013e3280115b7c] [PMID: 17211246]
[http://dx.doi.org/10.1161/01.HYP.0000159190.71253.c3] [PMID: 15753232]
[http://dx.doi.org/10.1038/sj.jhh.1001838] [PMID: 15729378]
[http://dx.doi.org/10.1097/HJH.0000000000000651] [PMID: 26114836]
[http://dx.doi.org/10.5551/jat.13.101] [PMID: 16733298]
[http://dx.doi.org/10.1093/eurheartj/suw062]
[http://dx.doi.org/10.1098/rspb.1922.0022]
[http://dx.doi.org/10.5551/jat.44834] [PMID: 30518727]
[http://dx.doi.org/10.1159/000445214] [PMID: 27493899]
[http://dx.doi.org/10.1291/hypres.31.1347] [PMID: 18957805]
[http://dx.doi.org/10.1093/ajh/hpw045] [PMID: 27143395]
[http://dx.doi.org/10.1016/0021-9290(80)90191-8] [PMID: 7364778]
[http://dx.doi.org/10.1136/bmj.i438] [PMID: 26868137]
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.12.005] [PMID: 22209214]
[http://dx.doi.org/10.1097/01.hjh.0000491627.59731.0f]
[http://dx.doi.org/10.1056/NEJMoa1504720] [PMID: 26378978]
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[http://dx.doi.org/10.1056/NEJMoa1611925] [PMID: 28605608]
[http://dx.doi.org/10.1016/j.ahj.2018.01.012] [PMID: 29898853]
[http://dx.doi.org/10.1186/s12933-017-0621-8] [PMID: 29061124]
[http://dx.doi.org/10.1186/s12933-018-0708-x] [PMID: 29703207]
[http://dx.doi.org/10.1186/s12933-017-0564-0] [PMID: 28683796]
[http://dx.doi.org/10.1210/jc.2019-00706] [PMID: 31162549]
[http://dx.doi.org/10.1111/dom.12572] [PMID: 26343814]
[http://dx.doi.org/10.1186/s12933-019-0839-8] [PMID: 30922297]
[http://dx.doi.org/10.1186/1475-2840-13-28] [PMID: 24475922]
[http://dx.doi.org/10.1186/s12933-018-0750-8] [PMID: 30060748]
[http://dx.doi.org/10.1186/s12933-017-0511-0] [PMID: 28241822]