Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

General Review Article

Diabetes Mellitus, Arterial Stiffness and Cardiovascular Disease: Clinical Implications and the Influence of SGLT2i

Author(s): Olga Lamacchia* and Maria Rosaria Sorrentino

Volume 19, Issue 2, 2021

Published on: 17 March, 2020

Page: [233 - 240] Pages: 8

DOI: 10.2174/1570161118666200317150359

Price: $65

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.

« Previous
Graphical Abstract
[1]
London GM, Pannier B. Arterial functions: how to interpret the complex physiology. Nephrol Dial Transplant 2010; 25(12): 3815-23.
[http://dx.doi.org/10.1093/ndt/gfq614] [PMID: 20947536]
[2]
Cocciolone AJ, Hawes JZ, Staiculescu MC, Johnson EO, Murshed M, Wagenseil JE. Elastin, arterial mechanics, and cardiovascular disease. Am J Physiol Heart Circ Physiol 2018; 315(2): H189-205.
[http://dx.doi.org/10.1152/ajpheart.00087.2018] [PMID: 29631368]
[3]
Wight T. The vascular extracellular matrix. Philadelphia, PA: Lippincott-Raven 1996.
[4]
Boutouyrie P, Fliser D, Goldsmith D, et al. Assessment of arterial stiffness for clinical and epidemiological studies: methodological con-siderations for validation and entry into the European Renal and Cardiovascular Medicine registry. Nephrol Dial Transplant 2014; 29(2): 232-9.
[http://dx.doi.org/10.1093/ndt/gft309] [PMID: 24084326]
[5]
Kucharska-Newton AM, Stoner L, Meyer ML. Determinants of vascular age: an epidemiological perspective. Clin Chem 2019; 65(1): 108-18.
[http://dx.doi.org/10.1373/clinchem.2018.287623] [PMID: 30459170]
[6]
Harvey A, Montezano AC, Lopes RA, Rios F, Touyz RM. Vascular fibrosis in aging and hypertension: molecular mechanisms and clinical implications. Can J Cardiol 2016; 32(5): 659-68.
[http://dx.doi.org/10.1016/j.cjca.2016.02.070] [PMID: 27118293]
[7]
O’Rourke MF. Principles and definitions of arterial stiffness, wave reflections and pulse pressure amplification. In: Handbook of hypertension Elsevier. 2006; 23: pp. 3-20.
[8]
Benetos A, Adamopoulos C, Bureau JM, et al. Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period. Circulation 2002; 105(10): 1202-7.
[http://dx.doi.org/10.1161/hc1002.105135] [PMID: 11889014]
[9]
McEniery CM, Wilkinson IB, Johansen NB, et al. Nondiabetic glucometabolic status and progression of aortic stiffness: the Whitehall II study. Diabetes Care 2017; 40: 599-60.
[http://dx.doi.org/10.2337/dc16-1773]
[10]
Brunner EJ, Shipley MJ, Ahmadi-Abhari S, et al. Adiposity, obesity, and arterial aging: longitudinal study of aortic stiffness in the Whitehall II cohort. Hypertension 2015; 66(2): 294-300.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05494] [PMID: 26056335]
[11]
McEniery CM, , Yasmin McDonnell B, et al. Anglo-Cardiff Collaborative Trial Investigators. Central pressure: variability and impact of cardiovascular risk factors: the Anglo-Cardiff Collaborative Trial II. Hypertension 2008; 51(6): 1476-82.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.105445] [PMID: 18426997]
[12]
Osborne-Pellegrin M, Labat C, Mercier N, Challande P, Lacolley P. Changes in aortic stiffness related to elastic fiber network anomalies in the Brown Norway rat during maturation and aging. Am J Physiol Heart Circ Physiol 2010; 299(1): H144-52.
[http://dx.doi.org/10.1152/ajpheart.00040.2010] [PMID: 20435849]
[13]
Yki-Järvinen H, Westerbacka J. Insulin resistance, arterial stiffness and wave reflection. Adv Cardiol 2007; 44: 252-60.
[http://dx.doi.org/10.1159/000096746] [PMID: 17075214]
[14]
Sutton-Tyrrell K, Newman A, Simonsick EM, et al. Aortic stiffness is associated with visceral adiposity in older adults enrolled in the study of health, aging, and body composition. Hypertension 2001; 38(3): 429-33.
[http://dx.doi.org/10.1161/01.HYP.38.3.429] [PMID: 11566917]
[15]
Gong J, Xie Q, Han Y, et al. Relationship between components of metabolic syndrome and arterial stiffness in Chinese hypertensives. Clin Exp Hypertens 2020; 42(2): 146-52.
[http://dx.doi.org/10.1080/10641963.2019.1590385] [PMID: 30964359]
[16]
Gajdova J, Karasek D, Goldmannova D, et al. Pulse wave analysis and diabetes mellitus. A systematic review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2017; 161(3): 223-33.
[http://dx.doi.org/10.5507/bp.2017.028] [PMID: 28627523]
[17]
Björntorp P. Metabolic implications of body fat distribution. Diabetes Care 1991; 14(12): 1132-43.
[http://dx.doi.org/10.2337/diacare.14.12.1132] [PMID: 1773700]
[18]
Egan BM, Lu G, Greene EL. Vascular effects of non-esterified fatty acids: implications for the cardiovascular risk factor cluster. Prostaglandins Leukot Essent Fatty Acids 1999; 60(5-6): 411-20.
[http://dx.doi.org/10.1016/S0952-3278(99)80022-2] [PMID: 10471131]
[19]
Ohyama Y, Teixido-Tura G, Ambale-Venkatesh B, et al. Ten-year longitudinal change in aortic stiffness assessed by cardiac MRI in the second half of the human lifespan: the multi-ethnic study of atherosclerosis. Eur Heart J Cardiovasc Imaging 2016; 17(9): 1044-53.
[http://dx.doi.org/10.1093/ehjci/jev332] [PMID: 26758407]
[20]
Ahmadi-Abhari S, Sabia S, Shipley MJ, et al. Physical activity, sedentary behavior, and long-term changes in aortic stiffness: the Whitehall II study. J Am Heart Assoc 2017; 6(8)e005974
[http://dx.doi.org/10.1161/JAHA.117.005974] [PMID: 28784651]
[21]
de Vegt F, Dekker JM, Ruhé HG, et al. Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia 1999; 42(8): 926-31.
[http://dx.doi.org/10.1007/s001250051249] [PMID: 10491751]
[22]
Duprez DA. Arterial stiffness and endothelial function: key players in vascular health. Hypertension 2010; 55(3): 612-3.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.144725] [PMID: 20083729]
[23]
Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375(9733): 2215-22.
[http://dx.doi.org/10.1016/S0140-6736(10)60484-9] [PMID: 20609967]
[24]
Laurent S, Cockcroft J, Van Bortel L, et al. European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27(21): 2588-605.
[http://dx.doi.org/10.1093/eurheartj/ehl254] [PMID: 17000623]
[25]
Gordin D, Groop PH. Aspects of hyperglycemia contribution to arterial stiffness and cardiovascular complications in patients with type 1 diabetes. J Diabetes Sci Technol 2016; 10(5): 1059-64.
[http://dx.doi.org/10.1177/1932296816636894] [PMID: 26956240]
[26]
Chirinos JA, Segers P, Gillebert TC, et al. Asklepios Investigators. Central pulse pressure and its hemodynamic determinants in middle-aged adults with impaired fasting glucose and diabetes: the Asklepios study. Diabetes Care 2013; 36(8): 2359-65.
[http://dx.doi.org/10.2337/dc12-1463] [PMID: 23610081]
[27]
Schram MT, Henry RMA, van Dijk RAJM, et al. Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes: the Hoorn Study. Hypertension 2004; 43(2): 176-81.
[http://dx.doi.org/10.1161/01.HYP.0000111829.46090.92] [PMID: 14698999]
[28]
Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA 1990; 263(21): 2893-8.
[http://dx.doi.org/10.1001/jama.1990.03440210043030] [PMID: 2338751]
[29]
Stehouwer CDA, Henry RMA, Ferreira I. Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia 2008; 51(4): 527-39.
[http://dx.doi.org/10.1007/s00125-007-0918-3] [PMID: 18239908]
[30]
Aronson D. Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. J Hypertens 2003; 21(1): 3-12.
[http://dx.doi.org/10.1097/00004872-200301000-00002] [PMID: 12544424]
[31]
Brillante DG, O’Sullivan AJ, Howes LG. Arterial stiffness in insulin resistance: the role of nitric oxide and angiotensin II receptors. Vasc Health Risk Manag 2009; 5(1): 73-8.
[PMID: 19436651]
[32]
Mackey RH, Venkitachalam L, Sutton-Tyrrell K. Calcifications, arterial stiffness and atherosclerosis. Adv Cardiol 2007; 44: 234-44.
[http://dx.doi.org/10.1159/000096744] [PMID: 17075212]
[33]
Basta G, Sironi AM, Lazzerini G, et al. Circulating soluble receptor for advanced glycation end products is inversely associated with glycemic control and S100A12 protein. J Clin Endocrinol Metab 2006; 91(11): 4628-34.
[http://dx.doi.org/10.1210/jc.2005-2559] [PMID: 16926247]
[34]
Di Pino A, Urbano F, Zagami RM, et al. Low endogenous secretory receptor for advanced glycation end-products levels are associated with inflammation and carotid atherosclerosis in prediabetes. J Clin Endocrinol Metab 2016; 101(4): 1701-9.
[http://dx.doi.org/10.1210/jc.2015-4069] [PMID: 26885882]
[35]
Tahara N, Yamagishi S, Matsui T, et al. Serum levels of advanced glycation end products (AGEs) are independent correlates of insulin resistance in nondiabetic subjects. Cardiovasc Ther 2012; 30(1): 42-8.
[http://dx.doi.org/10.1111/j.1755-5922.2010.00177.x] [PMID: 20626403]
[36]
Prenner SB, Chirinos JA. Arterial stiffness in diabetes mellitus. Atherosclerosis 2015; 238(2): 370-9.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.12.023] [PMID: 25558032]
[37]
Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39(2): 257-65.
[http://dx.doi.org/10.1016/S0735-1097(01)01746-6] [PMID: 11788217]
[38]
Thijssen DHJ, Bruno RM, van Mil ACCM, et al. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J 2019; 40(30): 2534-47.
[http://dx.doi.org/10.1093/eurheartj/ehz350] [PMID: 31211361]
[39]
Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American society of echocardiography carotid intima-media thickness task force. J Am Soc Echocardiogr 2008; 21(2): 93-111.
[http://dx.doi.org/10.1016/j.echo.2007.11.011] [PMID: 18261694]
[40]
Den Ruijter HM, Peters SA, Anderson TJ, et al. Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. JAMA 2012; 308(8): 796-803.
[http://dx.doi.org/10.1001/jama.2012.9630] [PMID: 22910757]
[41]
Chirinos JA. Arterial stiffness: basic concepts and measurement techniques. J Cardiovasc Transl Res 2012; 5(3): 243-55.
[http://dx.doi.org/10.1007/s12265-012-9359-6] [PMID: 22447229]
[42]
Creager MA, Lüscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I. Circulation 2003; 108(12): 1527-32.
[http://dx.doi.org/10.1161/01.CIR.0000091257.27563.32] [PMID: 14504252]
[43]
Lemogoum D, Flores G, Van den Abeele W, et al. Validity of pulse pressure and augmentation index as surrogate measures of arterial stiffness during beta-adrenergic stimulation. J Hypertens 2004; 22(3): 511-7.
[http://dx.doi.org/10.1097/00004872-200403000-00013] [PMID: 15076156]
[44]
Sakurai M, Yamakado T, Kurachi H, et al. The relationship between aortic augmentation index and pulse wave velocity: an invasive study. J Hypertens 2007; 25(2): 391-7.
[http://dx.doi.org/10.1097/HJH.0b013e3280115b7c] [PMID: 17211246]
[45]
Pannier B, Guérin AP, Marchais SJ, Safar ME, London GM. Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients. Hypertension 2005; 45(4): 592-6.
[http://dx.doi.org/10.1161/01.HYP.0000159190.71253.c3] [PMID: 15753232]
[46]
Sugawara J, Hayashi K, Yokoi T, et al. Brachial-ankle pulse wave velocity: an index of central arterial stiffness? J Hum Hypertens 2005; 19(5): 401-6.
[http://dx.doi.org/10.1038/sj.jhh.1001838] [PMID: 15729378]
[47]
Hayashi K, Yamamoto T, Takahara A, Shirai K. Clinical assessment of arterial stiffness with cardio-ankle vascular index: theory and applications. J Hypertens 2015; 33(9): 1742-57.
[http://dx.doi.org/10.1097/HJH.0000000000000651] [PMID: 26114836]
[48]
Shirai K, Utino J, Otsuka K, Takata M. A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb 2006; 13(2): 101-7.
[http://dx.doi.org/10.5551/jat.13.101] [PMID: 16733298]
[49]
Schillaci G, Battista F, D’Abbondanza M, Pucci G. The impact of the cardio‐ankle vascular index on left ventricular structure and function. Eur Heart J Suppl 2017; 19(Suppl. B): B30-4.
[http://dx.doi.org/10.1093/eurheartj/suw062]
[50]
Bramwell JC, Hill AV. The velocity of the pulse wave in man. Proc R Soc Lond, B 1922; 93: 298-306.
[http://dx.doi.org/10.1098/rspb.1922.0022]
[51]
Hasegawa M. Fundamental research on human aortic pulse wave velocity. Jikeikai Med J 1970; 85: 742-60.
[52]
Hasegawa M, Arai C. Clinical estimation of vascular elastic function and practical application. Connect Tissue 1995; 27: 149-57.
[53]
Takahashi K, Yamamoto T, Tsuda S, et al. Coefficients in the CAVI equation and the comparison between CAVI with and without the co-efficients using clinical data. J Atheroscler Thromb 2019; 26(5): 465-75.
[http://dx.doi.org/10.5551/jat.44834] [PMID: 30518727]
[54]
Miyoshi T, Ito H. Assessment of arterial stiffness using the cardio-ankle vascular index. Pulse (Basel) 2016; 4(1): 11-23.
[http://dx.doi.org/10.1159/000445214] [PMID: 27493899]
[55]
Takaki A, Ogawa H, Wakeyama T, et al. Cardio-ankle vascular index is superior to brachial-ankle pulse wave velocity as an index of arterial stiffness. Hypertens Res 2008; 31(7): 1347-55.
[http://dx.doi.org/10.1291/hypres.31.1347] [PMID: 18957805]
[56]
Lim J, Pearman M, Park W, Alkatan M, Tanaka H. Interrelationships among various measures of central artery stiffness. Am J Hypertens 2016; 29(9): 1024-8.
[http://dx.doi.org/10.1093/ajh/hpw045] [PMID: 27143395]
[57]
Hayashi K, Handa H, Nagasawa S, Okumura A, Moritake K. Stiffness and elastic behavior of human intracranial and extracranial arteries. J Biomech 1980; 13(2): 175-84.
[http://dx.doi.org/10.1016/0021-9290(80)90191-8] [PMID: 7364778]
[58]
Bangalore S, Fakheri R, Toklu B, Messerli FH. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials. BMJ 2016; 352: i438.
[http://dx.doi.org/10.1136/bmj.i438] [PMID: 26868137]
[59]
Shahin Y, Khan JA, Chetter I. Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials. Atherosclerosis 2012; 221(1): 18-33.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.12.005] [PMID: 22209214]
[60]
Mills CE, Govoni V, Faconti L, et al. Reducing arterial stiffness independently of blood pressure: Proof or concept? The randomized, facto-rial ‘VaSera’ trial. J Hypertens 2016; 30: 652-3.
[http://dx.doi.org/10.1097/01.hjh.0000491627.59731.0f]
[61]
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22): 2117-28.
[http://dx.doi.org/10.1056/NEJMoa1504720] [PMID: 26378978]
[62]
Marso SP, Daniels GH, Brown-Frandsen K, et al. LEADER Steering Committee. LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375(4): 311-22.
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[63]
Neal B, Perkovic V, Mahaffey KW, et al. CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7): 644-57.
[http://dx.doi.org/10.1056/NEJMoa1611925] [PMID: 28605608]
[64]
Wiviott SD, Raz I, Bonaca MP, et al. The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Trial. Am Heart J 2018; 200: 83-9.
[http://dx.doi.org/10.1016/j.ahj.2018.01.012] [PMID: 29898853]
[65]
Solini A, Giannini L, Seghieri M, et al. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol 2017; 16(1): 138.
[http://dx.doi.org/10.1186/s12933-017-0621-8] [PMID: 29061124]
[66]
Lee DM, Battson ML, Jarrell DK, et al. SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice. Cardiovasc Diabetol 2018; 17(1): 62.
[http://dx.doi.org/10.1186/s12933-018-0708-x] [PMID: 29703207]
[67]
Shigiyama F, Kumashiro N, Miyagi M, et al. Effectiveness of dapagliflozin on vascular endothelial function and glycemic control in patients with early-stage type 2 diabetes mellitus: DEFENCE study. Cardiovasc Diabetol 2017; 16(1): 84.
[http://dx.doi.org/10.1186/s12933-017-0564-0] [PMID: 28683796]
[68]
Solini A, Seghieri M, Giannini L, et al. The Effects of Dapagliflozin on Systemic and Renal Vascular Function Display an Epigenetic Sig-nature. J Clin Endocrinol Metab 2019; 104(10): 4253-63.
[http://dx.doi.org/10.1210/jc.2019-00706] [PMID: 31162549]
[69]
Chilton R, Tikkanen I, Cannon CP, et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab 2015; 17(12): 1180-93.
[http://dx.doi.org/10.1111/dom.12572] [PMID: 26343814]
[70]
Bosch A, Ott C, Jung S, et al. How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial. Cardiovasc Diabetol 2019; 18(1): 44.
[http://dx.doi.org/10.1186/s12933-019-0839-8] [PMID: 30922297]
[71]
Cherney DZ, Perkins BA, Soleymanlou N, et al. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol 2014; 13: 28.
[http://dx.doi.org/10.1186/1475-2840-13-28] [PMID: 24475922]
[72]
Aroor AR, Das NA, Carpenter AJ, et al. Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury. Cardiovasc Diabetol 2018; 17(1): 108.
[http://dx.doi.org/10.1186/s12933-018-0750-8] [PMID: 30060748]
[73]
Pfeifer M, Townsend RR, Davies MJ, Vijapurkar U, Ren J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol 2017; 16(1): 29.
[http://dx.doi.org/10.1186/s12933-017-0511-0] [PMID: 28241822]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy