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Current Vascular Pharmacology

Editor-in-Chief

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

Review Article

Effects of Lipid Lowering Drugs on Arterial Stiffness: One More Way to Reduce Cardiovascular Risk?

Author(s): Andromachi Reklou*, Niki Katsiki, Asterios Karagiannis and Vasilios Athyros

Volume 18, Issue 1, 2020

Page: [38 - 42] Pages: 5

DOI: 10.2174/1570161117666190121102323

Price: $65

Open Access Journals Promotions 2
Abstract

Arterial stiffness (AS) is considered an independent predictor of cardiovascular disease (CVD) events. Among lipid lowering drugs, statins have a beneficial effect on AS, independent of their hypolipidaemic effect. Based on 3 meta-analyses and other studies, this effect is compound- and doserelated. Potent statins at high doses are more effective than less powerful statins. Ezetimibe (± statin) also seems to decrease AS in patients with dyslipidaemia. Fibrates have no effect on AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have data that beneficially affect all AS risk factors, suggesting a beneficial effect on artery compliance. However, there is no direct measurement of their effect on AS indices. In patients with dyslipidaemia, prescribing high dose statins (± ezetimibe) will not only decrease low-density lipoprotein cholesterol levels but also improve AS (in addition to other effects). This effect on AS may contribute to the observed reduction in vascular events.

Keywords: Arterial stiffness, pulse wave velocity, augmentation index, statin, fibrate, ezetimibe, proprotein convertase subtilisin/ kexin type 9 (PCSK9), cardiovascular risk.

Graphical Abstract
[1]
Avolio A. Arterial stiffness. Pulse 2013; 1: 14-28.
[2]
Said MA, Eppinga RN, Lipsic E, Verweij N, van der Harst P. Relationship of arterial stiffness index and pulse pressure with cardiovascular disease and mortality. J Am Heart Assoc 2018; 7e007621
[3]
Townsend RR, Wilkinson IB, Schiffrin EL, et al. Recommendations for improving and standardizing vascular research on arterial stiffness: A scientific statement from the American heart association. Hypertension 2015; 66: 698-722.
[4]
Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. J Am Coll Cardiol 2010; 55: 1318-27.
[5]
Redheuil A, Wu CO, Kachenoura N, et al. Proximal aortic distensibility is an independent predictor of all-cause mortality and incident CV events: The MESA study. J Am Coll Cardiol 2014; 64: 2619-29.
[6]
Vlachopoulos C, Xaplanteris P, Aboyans V, et al. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European society of cardiology working group on peripheral circulation: Endorsed by the association for research into arterial structure and physiology (ARTERY) society. Atherosclerosis 2015; 241: 507-32.
[7]
Bonarjee VV. Arterial stiffness: a prognostic marker in coronary heart disease. Available methods and clinical application. Front Cardiovasc Med 2018; 5: 64.
[8]
Garcia-Ortiz L, Ramos-Delgado E, Recio-Rodriguez JI, et al. Peripheral and central arterial pressure and its relationship to vascular target organ damage in carotid artery, retina and arterial stiffness. Development and validation of a tool. The Vaso risk study. BMC Public Health 2011; 11: 266.
[9]
Janić M, Lunder M, Sabovič M. Arterial stiffness and cardiovascular therapy. BioMed Res Int 2014; 2014621437
[10]
D’elia L, La Fata E, Iannuzzi A, Rubba PO. Effect of statin therapy on pulse wave velocity: A meta-analysis of randomized controlled trials. Clin Exp Hypertens 2018; 40: 601-8.
[11]
Upala S, Wirunsawanya K, Jaruvongvanich V, Sanguankeo A. Effects of statin therapy on arterial stiffness: A systematic review and meta-analysis of randomized controlled trial. Int J Cardiol 2017; 227: 338-41.
[12]
Sahebkar A, Pećin I, Tedeschi-Reiner E, Derosa G, Maffioli P, Reiner Ž. Effects of statin therapy on augmentation index as a measure of arterial stiffness: A systematic review and meta-analysis. Int J Cardiol 2016; 212: 160-8.
[13]
Kanaki AI, Sarafidis PA, Georgianos PI, et al. Effects of low-dose atorvastatin on arterial stiffness and central aortic pressure augmentation in patients with hypertension and hypercholesterolemia. Am J Hypertens 2013; 26: 608-16.
[14]
Fassett RG, Robertson IK, Ball MJ, Geraghty DP, Sharman JE, Coombes JS. Effects of atorvastatin on arterial stiffness in chronic kidney disease: A randomised controlled trial. J Atheroscler Thromb 2010; 17: 235-41.
[15]
Sarafidis PA, Loutradis C, Karpetas A, et al. Ambulatory pulse wave velocity is a stronger predictor of cardiovascular events and all-cause mortality than office and ambulatory blood pressure in hemodialysis patients. Hypertension 2017; 70: 148-57.
[16]
Dogra G, Irish A, Chan D, Watts G. A randomized trial of the effect of statin and fibrate therapy on arterial function in CKD. Am J Kidney Dis 2007; 49: 776-85.
[17]
Lunder M, Janić M, Habjan S, Sabovič M. Subtherapeutic, low-dose fluvastatin improves functional and morphological arterial wall properties in apparently healthy, middle-aged males--a pilot study. Atherosclerosis 2011; 215: 446-51.
[18]
Wallace SM1 Mäki-Petäjä KM, Cheriyan J, et al. Simvastatin prevents inflammation-induced aortic stiffening and endothelial dysfunction. Br J Clin Pharmacol 2010; 70: 799-806.
[19]
Stoner L, Faulkner J, Lowe A, et al. Should the augmentation index be normalized to heart rate? J Atheroscler Thromb 2014; 21: 11-6.
[20]
Iketani T, Takazawa K, Yamashina A. Effect of eicosapentaenoic acid on central systolic blood pressure. Prostaglandins Leukot Essent Fatty Acids 2013; 88: 191-5.
[21]
Sunbul M, Agirbasli M, Durmus E, et al. Arterial stiffness in patients with non-alcoholic fatty liver disease is related to fibrosis stage and epicardial adipose tissue thickness. Atherosclerosis 2014; 237: 490-3.
[22]
Villela-Nogueira CA, Leite NC, Cardoso CR, Salles GF. NAFLD and increased aortic stiffness: Parallel or common physiopathological mechanisms? Int J Mol Sci 2016; 17pii: E460
[23]
Katsiki N, Imprialos K, Vlachopoulos C. Editorial: Arterial stiffness, central haemodynamics and non-alcoholic fatty liver disease: Links with cardiovascular risk and effects of drug treatment. Curr Vasc Pharmacol 2018; 16: 401-4.
[24]
Mitsiou E, Boutari C, Kotsis V, et al. Effect of low (5 mg) vs. high (20-40 mg) rosuvastatin dose on 24h arterial stiffness, central haemodynamics, and non-alcoholic fatty liver disease in patients with optimally controlled arterial hypertension. Curr Vasc Pharmacol 2018; 16: 393-400.
[25]
Elffers TW, Trompet S, de Mutsert R, et al. Borderline Q-waves in individuals without overt cardiovascular disease: Relations with adiposity, subclinical atherosclerosis and vascular stiffness. Int J Cardiol 2019; 274: 331-6.
[26]
Palombo C, Kozakova M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul Pharmacol 2016; 77: 1-7.
[27]
Raggi P. Epicardial adipose tissue as a marker of coronary artery disease risk. J Am Coll Cardiol 2013; 61: 1396-7.
[28]
Apovian CM, Bigornia S, Mott M, et al. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler Thromb Vasc Biol 2008; 28: 1654-9.
[29]
Koumaras C, Katsiki N, Athyros VG, Karagiannis A. Metabolic syndrome and arterial stiffness: the past, the present and the future. J Cardiovasc Med (Hagerstown) 2013; 14: 687-9.
[30]
de Heredia FP, Gomez-Martinez S, Marcos A. Obesity, inflammation and the immune system. Proc Nutr Soc 2012; 71: 332-8.
[31]
Park S, Lakatta EG. Role of inflammation in the pathogenesis of arterial stiffness. Yonsei Med J 2012; 53: 258-61.
[32]
Hajjar DP, Gotto AM Jr. Biological relevance of inflammation and oxidative stress in the pathogenesis of arterial diseases. Am J Pathol 2013; 182: 1474-81.
[33]
Tziomalos K, Athyros VG, Karagiannis A, Mikhailidis DP. Endothelial function, arterial stiffness and lipid lowering drugs. Expert Opin Ther Targets 2007; 11: 1143-60.
[34]
Egashira K, Hirooka Y, Kai H, et al. Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 1994; 89: 2519-24.
[35]
O’Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme reductase inhibitor, improves endothelial function within 1 month. Circulation 1997; 95: 1126-31.
[36]
Koh KK, Cardillo C, Bui MN, et al. Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women. Circulation 1999; 99: 354-60.
[37]
Lu TM, Ding YA, Leu HB, Yin WH, Sheu WH, Chu KM. Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in patients with hypercholesterolemia. Am J Cardiol 2004; 94: 157-61.
[38]
Alonso R, Mata P, De Andres R, Villacastin BP, Martinez-Gonzalez J, Badimon L. Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin. Atherosclerosis 2001; 157: 423-9.
[39]
Treasure CB, Klein JL, Weintraub WS, et al. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 1995; 332: 481-7.
[40]
Dupuis J, Tardif JC, Cernacek P, Theroux P. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (Reduction of cholesterol in ischemia and function of the endothelium) trial. Circulation 1999; 99: 3227-33.
[41]
Dupuis J, Tardif JC, Rouleau JL, et al. Intensity of lipid lowering with statins and brachial artery vascular endothelium reactivity after acute coronary syndromes (from the BRAVER trial). Am J Cardiol 2005; 96: 1207-13.
[42]
Murad F. Nitric oxide and cyclic GMP in cell signaling and drug development. N Engl J Med 2006; 355: 2003-11.
[43]
Szmitko PE, Wang C, Weisel RD, De Almeida JR, Anderson TJ, Verma S. New markers of inflammation and endothelial cell activation. Circulation 2003; 108: 1917-23.
[44]
Hare JM, Stamler JS. NO/redox disequilibrium in the failing heart and cardiovascular system. J Clin Invest 2005; 115: 509-17.
[45]
Matsuo T, Iwade K, Hirata N, et al. Improvement of arterial stiffness by the antioxidant and anti-inflammatory effects of short-term statin therapy in patients with hypercholesterolemia. Heart Vessels 2005; 20: 8-12.
[46]
Dilaveris P, Giannopoulos G, Riga M, Synetos A, Stefanadis C. Beneficial effects of statins on endothelial dysfunction and vascular stiffness. Curr Vasc Pharmacol 2007; 5: 227-37.
[47]
Ridker PM. From C-reactive protein to interleukin-6 to interleukin-1: Moving upstream to identify novel targets for atheroprotection. Circ Res 2016; 118: 145-56.
[48]
Lv S, Liu Y, Zou Z, et al. The impact of statins therapy on disease activity and inflammatory factor in patients with rheumatoid arthritis: a meta-analysis. Clin Exp Rheumatol 2015; 33: 69-76.
[49]
Li GM, Zhao J, Li B, et al. The anti-inflammatory effects of statins on patients with rheumatoid arthritis: A systemic review and meta-analysis of 15 randomized controlled trials. Autoimmun Rev 2018; 17: 215-25.
[50]
Efrati S, Averbukh M, Dishy V, Faygenzo M, Friedensohn L, Golik A. The effect of simvastatin, ezetimibe and their combination on the lipid profile, arterial stiffness and inflammatory markers. Eur J Clin Pharmacol 2007; 63: 113-21.
[51]
Colucci R, Fornai M, Duranti E, et al. Rosuvastatin prevents angiotensin II-induced vascular changes by inhibition of NAD(P)H oxidase and COX-1. Br J Pharmacol 2013; 169: 554-66.
[52]
Hanna IR, Taniyama Y, Szöcs K, Rocic P, Griendling KK. NAD(P)H oxidase-derived reactive oxygen species as mediators of angiotensin II signaling. Antioxid Redox Signal 2002; 4: 899-914.
[53]
Briones AM, Rodríguez-Criado N, Hernanz R, et al. Atorvastatin prevents angiotensin II-induced vascular remodeling and oxidative stress. Hypertension 2009; 54: 142-9.
[54]
Tissier F, Mallem Y, Goanvec C, et al. A non-hypocholesterolemic atorvastatin treatment improves vessel elasticity by acting on elastin composition in WHHL rabbits. Atherosclerosis 2016; 251: 70-7.
[55]
O’Rourke M. Mechanical principles in arterial disease. Hypertension 1995; 26: 2-9.
[56]
Kamberi LS, Gorani DR, Hoxha TF, Zahiti BF. Aortic compliance and stiffness among severe longstanding hypertensive and non-hypertensive. Acta Inform Med 2013; 21: 12-5.
[57]
Tsiara S, Elisaf M, Mikhailidis DP. Early vascular benefits of statin therapy. Curr Med Res Opin 2003; 19: 540-56.
[58]
Kurobe H, Aihara K, Higashida M. Ezetimibe monotherapy ameliorates vascular function in patients with hypercholesterolemia through decreasing oxidative stress. J Atheroscler Thromb 2011; 18: 1080-9.
[59]
Yagi S, Akaike M, Aihara K, et al. Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia. J Atheroscler Thromb 2010; 17: 173-80.
[60]
Nakagami H, Osako MK, Takami Y, et al. Vascular protective effects of ezetimibe in apoE-deficient mice. Atherosclerosis 2009; 203: 51-8.
[61]
Averna M. The effect of ezetimibe on NAFLD. Atheroscler Suppl 2015; 17: 27-34.
[62]
Wu NQ, Guo YL, Zhu CG, et al. Comparison of statin plus ezetimibe with double-dose statin on lipid profiles and inflammation markers. Lipids Health Dis 2018; Nov 23; 17: 265.
[63]
Tamaki N, Ueno H, Morinaga Y, Shiiya T, Nakazato M. Ezetimibe ameliorates atherosclerotic and inflammatory markers, atherogenic lipid profiles, insulin sensitivity, and liver dysfunction in Japanese patients with hypercholesterolemia. J Atheroscler Thromb 2012; 19: 532-8.
[64]
Hiramitsu S, Ishiguro Y, Matsuyama H, et al. The effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis in Japanese patients with dyslipidemia. J Atheroscler Thromb 2010; 17: 106-14.
[65]
Miyashita Y, Endo K, Saiki A, et al. Effect of ezetimibe monotherapy on lipid metabolism and arterial stiffness assessed by cardio-ankle vascular index in type 2 diabetic patients. J Atheroscler Thromb 2010; 17: 1070-6.
[66]
Mäki-Petäjä KM, Booth AD, Hall FC, et al. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll Cardiol 2007; 50: 852-8.
[67]
Marais AD. Familial hypercholesterolaemia. Clin Biochem Rev 2004; 25: 49-68.
[68]
Katsiki N, Athyros VG, Mikhailidis DP, Mantzoros C. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors: Shaping the future after the further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk (FOURIER) trial. Metabolism 2017; 74: 43-6.
[69]
Vincent J. Lipid lowering therapy for atherosclerotic cardiovascular disease: It is not so simple. Clin Pharmacol Ther 2018; 104: 220-4.
[70]
Vlachopoulos C, Koutagiar I, Terentes-Printzios D, et al. Relationship of PCSK9 levels with indices of vascular function and subclinical atherosclerosis in patients with familial dyslipidaemias. Hellenic J Cardiol 2019; 60(2): 124-8.
[71]
Rallidis LS, Lekakis J. PCSK9 inhibition as an emerging lipid lowering therapy: Unanswered questions. Hellenic J Cardiol 2016; 57: 86-91.
[72]
Cariouabc B, Maya C, Costetab P. Clinical aspects of PCSK9. Atherosclerosis 2011; 216: 258-65.
[73]
Wu H, Ballantyne CM. Dyslipidaemia: PCSK9 inhibitors and foamy monocytes in familial hypercholesterolaemia. Nat Rev Cardiol 2017; 14: 385-6.
[74]
Bernelot Moens SJ, Neele AE, Kroon J. PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia. Eur Heart J 2017; 38: 1584-93.
[75]
Cheng JM, Oemrawsingh RM, Garcia-Garcia HM, et al. PCSK9 in relation to coronary plaque inflammation: Results of the ATHEROREMO-IVUS study. Atherosclerosis 2016; 248: 117-22.
[76]
Gebauer K, Reinecke H. PCSK9 inhibition for LDL lowering and beyond - implications for patients with peripheral artery disease. Vasa 2018; 47: 165-76.
[77]
Puri R, Nissen SE, Somaratne R, et al. Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of global assessment of plaque regression with a pcsk9 antibody as measured by intravascular ultrasound (GLAGOV). Am Heart J 2016; 176: 83-92.
[78]
Nissen SE, Nicholls SJ. Results of the GLAGOV trial. Cleve Clin J Med 2017; 84(12): 1-5.
[79]
Cicero AF, Colletti A, Bajraktari G, et al. Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel. Nutr Rev 2017; 75: 731-67.
[80]
Reklou A, Doumas M, Imprialos K, Stavropoulos K, Patoulias D, Athyros VG. Reduction of vascular inflammation, ldl-c, or both for the protection from cardiovascular events? Open Cardiovasc Med J 2018; 12: 29-40.
[81]
Reklou A, Lazaridis A, Nikolaidou B, Kadiltzoglou P, Doumas M. Macro and microcirculation damage and incident hypertension: Predictors of progression? J Hypertens 2014; 32: 1154.

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