Pharmacy and Exercise as Complimentary Partners for Successful Cardiovascular Ageing

Page: [284 - 302] Pages: 19

  • * (Excluding Mailing and Handling)

Abstract

Diseases of the cardiovascular system have been the biggest cause of mortality for the majority of the last century, currently contributing to almost a third of deaths every year globally. Ageing associates with changes to the structure and function of the heart and vascular system that progressively increase the incidence of abnormalities, morbidity, and cardiovascular disease. The burden of ageing and its relationship to cardiovascular disease risk highlights the need for more research into the underlying mechanisms involved and how they may be treated and/or prevented. Factors influencing adrenergic dysfunction may explain a significant part of the age-related deterioration in health and responsiveness of the cardiovascular system. Increased sympathetic activity in old age overstimulates adrenergic receptors and causes detrimental changes within the associated signalling mechanisms, including a reduction in receptor number and downstream effector efficiency. Pharmacological agents, such as metformin, resveratrol, beta-blockers, and angiotensin converting enzyme (ACE) inhibitors, have been identified as potential anti-ageing therapies with cardiovascular effects, which may be beneficial in treating the decline in cardiovascular function with old age. Regular exercise has also shown promise in the prevention and treatment of harmful age-related effects on the cardiovascular system. This review will investigate age-associated vascular and cardiac remodelling, and the link between adrenergic dysfunction and vascular and cardiac control. This review will also consider whether pharmacological or non-pharmacological therapies are most effective, or indeed complimentary to potentially optimised ageing of the cardiovascular system and improved quality of life in the elderly.

Keywords: Ageing, anti-ageing, adrenergic receptor signalling, cardiovascular remodelling, vascular health, exercise training.

Graphical Abstract

[1]
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]
[2]
Vial G, Detaille D, Guigas B. Role of mitochondria in the mechanism (s) of action of metformin. Front Endocrinol (Lausanne) 2019; 10: 294.
[http://dx.doi.org/10.3389/fendo.2019.00294] [PMID: 31133988]
[3]
Ferrara N, Komici K, Corbi G, et al. β-adrenergic receptor responsiveness in aging heart and clinical implications. Front Physiol 2014; 4: 396.
[http://dx.doi.org/10.3389/fphys.2013.00396] [PMID: 24409150]
[4]
Mathers CD, Stevens GA, Boerma T, White RA, Tobias MI. Causes of international increases in older age life expectancy. Lancet 2015; 385(9967): 540-8.
[http://dx.doi.org/10.1016/S0140-6736(14)60569-9] [PMID: 25468166]
[5]
Roser M, Ritchie H, Ortiz-Ospina E. Our world in data, 2013. World population growth 2013.
[6]
Organization WH. World health statistics 2019: monitoring health for the SDGs, sustainable development goals. 2019.
[7]
Pyrkov TV, Avchaciov K, Tarkhov AE, Menshikov LI, Gudkov AV, Fedichev PO. Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit. Nat Commun 2021; 12(1): 2765.
[http://dx.doi.org/10.1038/s41467-021-23014-1] [PMID: 34035236]
[8]
Raleigh V. What is happening to life expectancy in the UK. England The King’s Fund 2019.
[9]
Marmot M. Health equity in England: the Marmot review 10 years on. BMJ 2020; 368: m693.
[http://dx.doi.org/10.1136/bmj.m693] [PMID: 32094110]
[10]
Randall M. Overview of the UK population: July 2017. UK Office for national statistics (July 2017). 2017.
[11]
de Beer J, Bardoutsos A, Janssen F. Maximum human lifespan may increase to 125 years. Nature 2017; 546(7660): E16-7.
[http://dx.doi.org/10.1038/nature22792] [PMID: 28658213]
[12]
Rozing MP, Kirkwood TBL, Westendorp RGJ. Is there evidence for a limit to human lifespan? Nature 2017; 546(7660): E11-2.
[http://dx.doi.org/10.1038/nature22788] [PMID: 28658235]
[13]
Lenart A, Vaupel JW. Questionable evidence for a limit to human lifespan. Nature 2017; 546(7660): E13-4.
[http://dx.doi.org/10.1038/nature22790] [PMID: 28658239]
[14]
Dong X, Milholland B, Vijg J. Evidence for a limit to human lifespan. Nature 2016; 538(7624): 257-9.
[http://dx.doi.org/10.1038/nature19793] [PMID: 27706136]
[15]
Crimmins EM. Lifespan and healthspan: past, present, and promise. Gerontologist 2015; 55(6): 901-11.
[http://dx.doi.org/10.1093/geront/gnv130] [PMID: 26561272]
[16]
Niccoli T, Partridge L. Ageing as a risk factor for disease. Curr Biol 2012; 22(17): R741-52.
[http://dx.doi.org/10.1016/j.cub.2012.07.024] [PMID: 22975005]
[17]
Santulli G, Iaccarino G. Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes. Immun Ageing 2013; 10(1): 10.
[http://dx.doi.org/10.1186/1742-4933-10-10] [PMID: 23497413]
[18]
de Lucia C, Eguchi A, Koch WJ. New insights in cardiac β-adrenergic signaling during heart failure and aging. Front Pharmacol 2018; 9: 904.
[http://dx.doi.org/10.3389/fphar.2018.00904] [PMID: 30147654]
[19]
Maron BJ, Pelliccia A. The heart of trained athletes: cardiac remodeling and the risks of sports, including sudden death. Circulation 2006; 114(15): 1633-44.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.613562] [PMID: 17030703]
[20]
Barnes RF, Raskind M, Gumbrecht G, Halter JB. The effects of age on the plasma catecholamine response to mental stress in man. J Clin Endocrinol Metab 1982; 54(1): 64-9.
[http://dx.doi.org/10.1210/jcem-54-1-64] [PMID: 7054219]
[21]
Fleg JL, Tzankoff SP, Lakatta EG. Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males. J Appl Physiol 1985; 59(4): 1033-9.
[http://dx.doi.org/10.1152/jappl.1985.59.4.1033] [PMID: 4055584]
[22]
Aalami OO, Fang TD, Song HM, Nacamuli RP. Physiological features of aging persons. Arch Surg 2003; 138(10): 1068-76.
[http://dx.doi.org/10.1001/archsurg.138.10.1068] [PMID: 14557122]
[23]
Nagaratnam N. Ageing and Longevity.Advanced Age Geriatric Care. Springer 2019; pp. 3-9.
[http://dx.doi.org/10.1007/978-3-319-96998-5_1]
[24]
Jin K. Modern biological theories of aging. Aging Dis 2010; 1(2): 72-4.
[PMID: 21132086]
[25]
Hayflick L. Theories of biological aging. Exp Gerontol 1985; 20(3-4): 145-59.
[http://dx.doi.org/10.1016/0531-5565(85)90032-4] [PMID: 3905424]
[26]
Bwiza CP, Son JM, Lee C. Integrated theories of biological aging. Oxford Research Encyclopedia of Psychology. 2019.
[http://dx.doi.org/10.1093/acrefore/9780190236557.013.334]
[27]
Andersson C, Vasan RS. Epidemiology of cardiovascular disease in young individuals. Nat Rev Cardiol 2018; 15(4): 230-40.
[http://dx.doi.org/10.1038/nrcardio.2017.154] [PMID: 29022571]
[28]
Wilkins E, Wilson L, Wickramasinghe K, et al. European cardiovascular disease statistics 2017. 2017.
[29]
Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res 1991; 68(6): 1560-8.
[http://dx.doi.org/10.1161/01.RES.68.6.1560] [PMID: 2036710]
[30]
Sheydina A, Riordon DR, Boheler KR. Molecular mechanisms of cardiomyocyte aging. Clin Sci (Lond) 2011; 121(8): 315-29.
[http://dx.doi.org/10.1042/CS20110115] [PMID: 21699498]
[31]
Gurven M, Blackwell AD, Rodríguez DE, Stieglitz J, Kaplan H. Does blood pressure inevitably rise with age?: longitudinal evidence among forager-horticulturalists. Hypertension 2012; 60(1): 25-33.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.189100] [PMID: 22700319]
[32]
Pearson JD, Morrell CH, Brant LJ, Landis PK, Fleg JL. Age-associated changes in blood pressure in a longitudinal study of healthy men and women. J Gerontol A Biol Sci Med Sci 1997; 52(3): M177-83.
[http://dx.doi.org/10.1093/gerona/52A.3.M177] [PMID: 9158560]
[33]
Ferrari AU, Radaelli A, Centola M. Invited review: aging and the cardiovascular system. J Appl Physiol 2003; 95(6): 2591-7.
[http://dx.doi.org/10.1152/japplphysiol.00601.2003] [PMID: 14600164]
[34]
Dai D-F, Chen T, Johnson SC, Szeto H, Rabinovitch PS. Cardiac aging: from molecular mechanisms to significance in human health and disease. Antioxid Redox Signal 2012; 16(12): 1492-526.
[http://dx.doi.org/10.1089/ars.2011.4179] [PMID: 22229339]
[35]
Shin E, Ko KS, Rhee BD, Han J, Kim N. Different effects of prolonged β-adrenergic stimulation on heart and cerebral artery. Integr Med Res 2014; 3(4): 204-10.
[http://dx.doi.org/10.1016/j.imr.2014.10.002] [PMID: 28664099]
[36]
Shimizu I, Minamino T. Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol 2016; 97: 245-62.
[http://dx.doi.org/10.1016/j.yjmcc.2016.06.001] [PMID: 27262674]
[37]
Backs J, Song K, Bezprozvannaya S, Chang S, Olson EN. CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J Clin Invest 2006; 116(7): 1853-64.
[http://dx.doi.org/10.1172/JCI27438] [PMID: 16767219]
[38]
Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol 2018; 15(7): 387-407.
[http://dx.doi.org/10.1038/s41569-018-0007-y] [PMID: 29674714]
[39]
Wilkins BJ, Molkentin JD. Calcium-calcineurin signaling in the regulation of cardiac hypertrophy. Biochem Biophys Res Commun 2004; 322(4): 1178-91.
[http://dx.doi.org/10.1016/j.bbrc.2004.07.121] [PMID: 15336966]
[40]
Chacar S, Hajal J, Saliba Y, et al. Long-term intake of phenolic compounds attenuates age-related cardiac remodeling. Aging Cell 2019; 18(2): e12894.
[http://dx.doi.org/10.1111/acel.12894] [PMID: 30680911]
[41]
Anversa P, Hiler B, Ricci R, Guideri G, Olivetti G. Myocyte cell loss and myocyte hypertrophy in the aging rat heart. J Am Coll Cardiol 1986; 8(6): 1441-8.
[http://dx.doi.org/10.1016/S0735-1097(86)80321-7] [PMID: 2946746]
[42]
Manne N, Kakarla S, Arvapalli R, Rice K, Blough E. Molecular mechanisms of age-related cardiac hypertrophy in the F344XBN rat model. J Clin Exp Cardiolog 2014; 5: 2.
[43]
Gerdts E, Roman MJ, Palmieri V, et al. Impact of age on left ventricular hypertrophy regression during antihypertensive treatment with losartan or atenolol (the LIFE study). J Hum Hypertens 2004; 18(6): 417-22.
[http://dx.doi.org/10.1038/sj.jhh.1001718] [PMID: 15103312]
[44]
Lindsey ML, Goshorn DK, Squires CE, et al. Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function. Cardiovasc Res 2005; 66(2): 410-9.
[http://dx.doi.org/10.1016/j.cardiores.2004.11.029] [PMID: 15820210]
[45]
Strait JB, Lakatta EG. Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 2012; 8(1): 143-64.
[http://dx.doi.org/10.1016/j.hfc.2011.08.011] [PMID: 22108734]
[46]
Ungvari Z, Tarantini S, Donato AJ, Galvan V, Csiszar A. Mechanisms of vascular aging. Circ Res 2018; 123(7): 849-67.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.311378] [PMID: 30355080]
[47]
Fares E, Howlett SE. Effect of age on cardiac excitation-contraction coupling. Clin Exp Pharmacol Physiol 2010; 37(1): 1-7.
[http://dx.doi.org/10.1111/j.1440-1681.2009.05276.x] [PMID: 19671063]
[48]
Zhu X, Altschafl BA, Hajjar RJ, Valdivia HH, Schmidt U. Altered Ca2+ sparks and gating properties of ryanodine receptors in aging cardiomyocytes. Cell Calcium 2005; 37(6): 583-91.
[http://dx.doi.org/10.1016/j.ceca.2005.03.002] [PMID: 15862349]
[49]
Jiang MT, Narayanan N. Effects of aging on phospholamban phosphorylation and calcium transport in rat cardiac sarcoplasmic reticulum. Mech Ageing Dev 1990; 54(1): 87-101.
[http://dx.doi.org/10.1016/0047-6374(90)90018-B] [PMID: 2366595]
[50]
Lim CC, Liao R, Varma N, Apstein CS. Impaired lusitropy-frequency in the aging mouse: role of Ca(2+)-handling proteins and effects of isoproterenol. Am J Physiol 1999; 277(5): H2083-90.
[PMID: 10564164]
[51]
Liu J, Sirenko S, Juhaszova M, et al. Age-associated abnormalities of intrinsic automaticity of sinoatrial nodal cells are linked to deficient cAMP-PKA-Ca(2+) signaling. Am J Physiol Heart Circ Physiol 2014; 306(10): H1385-97.
[http://dx.doi.org/10.1152/ajpheart.00088.2014] [PMID: 24633551]
[52]
Liu SJ, Wyeth RP, Melchert RB, Kennedy RH. Aging-associated changes in whole cell K(+) and L-type Ca(2+) currents in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 2000; 279(3): H889-900.
[http://dx.doi.org/10.1152/ajpheart.2000.279.3.H889] [PMID: 10993747]
[53]
Walker KE, Lakatta EG, Houser SR. Age associated changes in membrane currents in rat ventricular myocytes. Cardiovasc Res 1993; 27(11): 1968-77.
[http://dx.doi.org/10.1093/cvr/27.11.1968] [PMID: 8287405]
[54]
Feridooni HA, Dibb KM, Howlett SE. How cardiomyocyte excitation, calcium release and contraction become altered with age. J Mol Cell Cardiol 2015; 83: 62-72.
[http://dx.doi.org/10.1016/j.yjmcc.2014.12.004] [PMID: 25498213]
[55]
Josephson IR, Guia A, Stern MD, Lakatta EG. Alterations in properties of L-type Ca channels in aging rat heart. J Mol Cell Cardiol 2002; 34(3): 297-308.
[http://dx.doi.org/10.1006/jmcc.2001.1512] [PMID: 11945022]
[56]
Ocorr K, Reeves NL, Wessells RJ, et al. KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging. Proc Natl Acad Sci USA 2007; 104(10): 3943-8.
[http://dx.doi.org/10.1073/pnas.0609278104] [PMID: 17360457]
[57]
Harvey A, Montezano AC, Touyz RM. Vascular biology of ageing-Implications in hypertension. J Mol Cell Cardiol 2015; 83: 112-21.
[http://dx.doi.org/10.1016/j.yjmcc.2015.04.011] [PMID: 25896391]
[58]
Albarwani SA, Mansour F, Khan AA, et al. Aging reduces L-type calcium channel current and the vasodilatory response of small mesenteric arteries to calcium channel blockers. Front Physiol 2016; 7: 171.
[http://dx.doi.org/10.3389/fphys.2016.00171] [PMID: 27242545]
[59]
Taddei S, Virdis A, Ghiadoni L, et al. Age-related reduction of NO availability and oxidative stress in humans. Hypertension 2001; 38(2): 274-9.
[http://dx.doi.org/10.1161/01.HYP.38.2.274] [PMID: 11509489]
[60]
Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 1994; 24(2): 471-6.
[http://dx.doi.org/10.1016/0735-1097(94)90305-0] [PMID: 8034885]
[61]
Taddei S, Virdis A, Mattei P, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 1995; 91(7): 1981-7.
[http://dx.doi.org/10.1161/01.CIR.91.7.1981] [PMID: 7895356]
[62]
Donato AJ, Eskurza I, Silver AE, et al. Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB. Circ Res 2007; 100(11): 1659-66.
[http://dx.doi.org/10.1161/01.RES.0000269183.13937.e8] [PMID: 17478731]
[63]
Upadhya B, Taffet GE, Cheng CP, Kitzman DW. Heart failure with preserved ejection fraction in the elderly: scope of the problem. J Mol Cell Cardiol 2015; 83: 73-87.
[http://dx.doi.org/10.1016/j.yjmcc.2015.02.025] [PMID: 25754674]
[64]
Nakou ES, Parthenakis FI, Kallergis EM, Marketou ME, Nakos KS, Vardas PE. Healthy aging and myocardium: a complicated process with various effects in cardiac structure and physiology. Int J Cardiol 2016; 209: 167-75.
[http://dx.doi.org/10.1016/j.ijcard.2016.02.039] [PMID: 26896615]
[65]
Christou DD, Seals DR. Decreased maximal heart rate with aging is related to reduced β-adrenergic responsiveness but is largely explained by a reduction in intrinsic heart rate. J Appl Physiol 2008; 105(1): 24-9.
[http://dx.doi.org/10.1152/japplphysiol.90401.2008] [PMID: 18483165]
[66]
Stratton JR, Levy WC, Caldwell JH, et al. Effects of aging on cardiovascular responses to parasympathetic withdrawal. Age 2003; 41: 2077-83.
[67]
Huang X, Yang P, Du Y, Zhang J, Ma A. Age-related down-regulation of HCN channels in rat sinoatrial node. Basic Res Cardiol 2007; 102(5): 429-35.
[http://dx.doi.org/10.1007/s00395-007-0660-5] [PMID: 17572839]
[68]
Larson ED, St Clair JR, Sumner WA, Bannister RA, Proenza C. Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate. Proc Natl Acad Sci USA 2013; 110(44): 18011-6.
[http://dx.doi.org/10.1073/pnas.1308477110] [PMID: 24128759]
[69]
Jones SA, Boyett MR, Lancaster MK. Declining into failure: the age-dependent loss of the L-type calcium channel within the sinoatrial node. Circulation 2007; 115(10): 1183-90.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.663070] [PMID: 17339548]
[70]
Roh J, Rhee J, Chaudhari V, Rosenzweig A. The role of exercise in cardiac aging: from physiology to molecular mechanisms. Circ Res 2016; 118(2): 279-95.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.305250] [PMID: 26838314]
[71]
Jones SA, Lancaster MK, Boyett MR. Ageing-related changes of connexins and conduction within the sinoatrial node. J Physiol 2004; 560(Pt 2): 429-37.
[http://dx.doi.org/10.1113/jphysiol.2004.072108] [PMID: 15308686]
[72]
Howlett LA, Lancaster MK. Reduced cardiac response to the adrenergic system is a key limiting factor for physical capacity in old age. Exp Gerontol 2021; 150: 111339.
[http://dx.doi.org/10.1016/j.exger.2021.111339] [PMID: 33838216]
[73]
Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. Cardiac fibrosis: the fibroblast awakens. Circ Res 2016; 118(6): 1021-40.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306565] [PMID: 26987915]
[74]
Liu T, Song D, Dong J, et al. Current understanding of the pathophysiology of myocardial fibrosis and its quantitative assessment in heart failure. Front Physiol 2017; 8: 238.
[http://dx.doi.org/10.3389/fphys.2017.00238] [PMID: 28484397]
[75]
Trial J, Cieslik KA. Changes in cardiac resident fibroblast physiology and phenotype in aging. Am J Physiol Heart Circ Physiol 2018; 315(4): H745-55.
[http://dx.doi.org/10.1152/ajpheart.00237.2018] [PMID: 29906228]
[76]
Steenman M, Lande G. Cardiac aging and heart disease in humans. Biophys Rev 2017; 9(2): 131-7.
[http://dx.doi.org/10.1007/s12551-017-0255-9] [PMID: 28510085]
[77]
Chaudhary KR, El-Sikhry H, Seubert JM. Mitochondria and the aging heart. J Geriatr Cardiol 2011; 8(3): 159-67.
[http://dx.doi.org/10.3724/SP.J.1263.2011.00159] [PMID: 22783302]
[78]
Trott DW, Fadel PJ. Inflammation as a mediator of arterial ageing. Exp Physiol 2019; 104(10): 1455-71.
[http://dx.doi.org/10.1113/EP087499] [PMID: 31325339]
[79]
Wu J, Xia S, Kalionis B, Wan W, Sun T. The role of oxidative stress and inflammation in cardiovascular aging. BioMed Res Int 2014; 2014.
[http://dx.doi.org/10.1155/2014/615312]
[80]
Lakatta EG. Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons. Heart Fail Rev 2002; 7(1): 29-49.
[http://dx.doi.org/10.1023/A:1013797722156] [PMID: 11790921]
[81]
Fleg JL, Strait J. Age-associated changes in cardiovascular structure and function: a fertile milieu for future disease. Heart Fail Rev 2012; 17(4-5): 545-54.
[http://dx.doi.org/10.1007/s10741-011-9270-2] [PMID: 21809160]
[82]
Uejima T, Dunstan FD, Arbustini E, et al. E-Tracking International Collaboration Group (ETIC). Age-specific reference values for carotid arterial stiffness estimated by ultrasonic wall tracking. J Hum Hypertens 2020; 34(3): 214-22.
[http://dx.doi.org/10.1038/s41371-019-0228-5] [PMID: 31435004]
[83]
Chantler PD, Lakatta EG. Arterial-ventricular coupling with aging and disease. Front Physiol 2012; 3: 90.
[http://dx.doi.org/10.3389/fphys.2012.00090] [PMID: 22586401]
[84]
Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 1975; 56(1): 56-64.
[http://dx.doi.org/10.1172/JCI108079] [PMID: 124746]
[85]
Houghton D, Jones TW, Cassidy S, et al. The effect of age on the relationship between cardiac and vascular function. Mech Ageing Dev 2016; 153: 1-6.
[http://dx.doi.org/10.1016/j.mad.2015.11.001] [PMID: 26590322]
[86]
Lakatta EG, Sollott SJ. Perspectives on mammalian cardiovascular aging: humans to molecules. Comp Biochem Physiol A Mol Integr Physiol 2002; 132(4): 699-721.
[http://dx.doi.org/10.1016/S1095-6433(02)00124-1] [PMID: 12095857]
[87]
Borlaug BA, Lam CS, Roger VL, Rodeheffer RJ, Redfield MM. Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction. J Am Coll Cardiol 2009; 54(5): 410-8.
[http://dx.doi.org/10.1016/j.jacc.2009.05.013] [PMID: 19628115]
[88]
Sonaglioni A, Baravelli M, Lombardo M, et al. Ventricular-arterial coupling in centenarians without cardiovascular diseases. Aging Clin Exp Res 2018; 30(4): 367-73.
[http://dx.doi.org/10.1007/s40520-017-0783-y] [PMID: 28616854]
[89]
Najjar SS, Schulman SP, Gerstenblith G, et al. Age and gender affect ventricular-vascular coupling during aerobic exercise. J Am Coll Cardiol 2004; 44(3): 611-7.
[http://dx.doi.org/10.1016/j.jacc.2004.04.041] [PMID: 15358029]
[90]
Tellez JO, Mczewski M, Yanni J, et al. Ageing-dependent remodelling of ion channel and Ca2+ clock genes underlying sino-atrial node pacemaking. Exp Physiol 2011; 96(11): 1163-78.
[http://dx.doi.org/10.1113/expphysiol.2011.057752] [PMID: 21724736]
[91]
Davies CH, Ferrara N, Harding SE. β-adrenoceptor function changes with age of subject in myocytes from non-failing human ventricle. Cardiovasc Res 1996; 31(1): 152-6.
[PMID: 8849600]
[92]
Najafi A, Sequeira V, Kuster DW, van der Velden J. β-adrenergic receptor signalling and its functional consequences in the diseased heart. Eur J Clin Invest 2016; 46(4): 362-74.
[http://dx.doi.org/10.1111/eci.12598] [PMID: 26842371]
[93]
Narayanan N, Derby J-A. Alterations in the properties of β-adrenergic receptors of myocardial membranes in aging: impairments in agonist-receptor interactions and guanine nucleotide regulation accompany diminished catecholamine-responsiveness of adenylate cyclase. Mech Ageing Dev 1982; 19(2): 127-39.
[http://dx.doi.org/10.1016/0047-6374(82)90004-5] [PMID: 6287123]
[94]
White M, Roden R, Minobe W, et al. Age-related changes in beta-adrenergic neuroeffector systems in the human heart. Circulation 1994; 90(3): 1225-38.
[http://dx.doi.org/10.1161/01.CIR.90.3.1225] [PMID: 8087932]
[95]
Ungerer M, Böhm M, Elce JS, Erdmann E, Lohse MJ. Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart. Circulation 1993; 87(2): 454-63.
[http://dx.doi.org/10.1161/01.CIR.87.2.454] [PMID: 8381058]
[96]
Xiao R-P, Spurgeon HA, O’Connor F, Lakatta EG. Age-associated changes in beta-adrenergic modulation on rat cardiac excitation-contraction coupling. J Clin Invest 1994; 94(5): 2051-9.
[http://dx.doi.org/10.1172/JCI117559] [PMID: 7962551]
[97]
Farrell SR, Howlett SE. The age-related decrease in catecholamine sensitivity is mediated by beta(1)-adrenergic receptors linked to a decrease in adenylate cyclase activity in ventricular myocytes from male Fischer 344 rats. Mech Ageing Dev 2008; 129(12): 735-44.
[http://dx.doi.org/10.1016/j.mad.2008.09.017] [PMID: 18973772]
[98]
Scarpace PJ, Tumer N, Mader SL. β-adrenergic function in aging. Basic mechanisms and clinical implications. Drugs Aging 1991; 1(2): 116-29.
[http://dx.doi.org/10.2165/00002512-199101020-00004] [PMID: 1665371]
[99]
Tobise K, Ishikawa Y, Holmer SR, et al. Changes in type VI adenylyl cyclase isoform expression correlate with a decreased capacity for cAMP generation in the aging ventricle. Circ Res 1994; 74(4): 596-603.
[http://dx.doi.org/10.1161/01.RES.74.4.596] [PMID: 8137496]
[100]
Spadari RC, Cavadas C, de Carvalho AETS, Ortolani D, de Moura AL, Vassalo PF. Role of beta-adrenergic receptors and sirtuin signaling in the heart during aging, heart failure, and adaptation to stress. Cell Mol Neurobiol 2018; 38(1): 109-20.
[http://dx.doi.org/10.1007/s10571-017-0557-2] [PMID: 29063982]
[101]
Marín J. Age-related changes in vascular responses: a review. Mech Ageing Dev 1995; 79(2-3): 71-114.
[http://dx.doi.org/10.1016/0047-6374(94)01551-V] [PMID: 7616768]
[102]
Jensen BC, O’Connell TD, Simpson PC. Alpha-1-adrenergic receptors: targets for agonist drugs to treat heart failure. J Mol Cell Cardiol 2011; 51(4): 518-28.
[http://dx.doi.org/10.1016/j.yjmcc.2010.11.014] [PMID: 21118696]
[103]
O’Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev 2013; 66(1): 308-33.
[http://dx.doi.org/10.1124/pr.112.007203] [PMID: 24368739]
[104]
Garcia MI, Boehning D. Cardiac inositol 1,4,5-trisphosphate receptors. Biochim Biophys Acta Mol Cell Res 2017; 1864(6): 907-14.
[http://dx.doi.org/10.1016/j.bbamcr.2016.11.017] [PMID: 27884701]
[105]
Graham RM, Perez DM, Hwa J, Piascik MT. α 1-adrenergic receptor subtypes. Molecular structure, function, and signaling. Circ Res 1996; 78(5): 737-49.
[http://dx.doi.org/10.1161/01.RES.78.5.737] [PMID: 8620593]
[106]
Michelotti GA, Price DT, Schwinn DA. α 1-adrenergic receptor regulation: basic science and clinical implications. Pharmacol Ther 2000; 88(3): 281-309.
[http://dx.doi.org/10.1016/S0163-7258(00)00092-9] [PMID: 11337028]
[107]
Cupitra NI, Calderón JC, Narvaez-Sanchez R. Influence of ageing on vascular reactivity and receptor expression in rabbit aorta: a complement to elastocalcinosis and smooth muscle mechanisms. Clin Interv Aging 2020; 15: 537-45.
[http://dx.doi.org/10.2147/CIA.S236173] [PMID: 32368020]
[108]
Su N, Narayanan N. Age related alteration in cholinergic but not α adrenergic response of rat coronary vasculature. Cardiovasc Res 1993; 27(2): 284-90.
[http://dx.doi.org/10.1093/cvr/27.2.284] [PMID: 8097134]
[109]
Zhang J, Simpson PC, Jensen BC. Cardiac α1A-adrenergic receptors: emerging protective roles in cardiovascular diseases. Am J Physiol Heart Circ Physiol 2021; 320(2): H725-33.
[http://dx.doi.org/10.1152/ajpheart.00621.2020] [PMID: 33275531]
[110]
Korzick DH, Holiman DA, Boluyt MO, Laughlin MH, Lakatta EG. Diminished α1-adrenergic-mediated contraction and translocation of PKC in senescent rat heart. Am J Physiol Heart Circ Physiol 2001; 281(2): H581-9.
[http://dx.doi.org/10.1152/ajpheart.2001.281.2.H581] [PMID: 11454560]
[111]
White M, Fourney A, Mikes E, Leenen FH. Effects of age and hypertension on cardiac responses to the α1-agonist phenylephrine in humans. Am J Hypertens 1999; 12(2 Pt 1): 151-8.
[http://dx.doi.org/10.1016/S0895-7061(98)00220-9] [PMID: 10090342]
[112]
Giovannitti JA Jr, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog 2015; 62(1): 31-9.
[http://dx.doi.org/10.2344/0003-3006-62.1.31] [PMID: 25849473]
[113]
Smith EG, Voyles WF, Kirby BS, Markwald RR, Dinenno FA. Ageing and leg postjunctional α-adrenergic vasoconstrictor responsiveness in healthy men. J Physiol 2007; 582(Pt 1): 63-71.
[http://dx.doi.org/10.1113/jphysiol.2007.130591] [PMID: 17463044]
[114]
Madamanchi A. β-adrenergic receptor signaling in cardiac function and heart failure. McGill J Med 2007; 10(2): 99-104.
[PMID: 18523538]
[115]
Johnson M. Beta2-adrenoceptors: mechanisms of action of beta2-agonists. Paediatr Respir Rev 2001; 2(1): 57-62.
[http://dx.doi.org/10.1053/prrv.2000.0102] [PMID: 16263481]
[116]
Billington CK, Penn RB, Hall IP. β 2 agonists. Pharmacol Therapeut Asthma COPD 2016; 23-40.
[117]
Xiao R-P, Tomhave ED, Wang D-J, et al. Age-associated reductions in cardiac beta1- and beta2-adrenergic responses without changes in inhibitory G proteins or receptor kinases. J Clin Invest 1998; 101(6): 1273-82.
[http://dx.doi.org/10.1172/JCI1335] [PMID: 9502768]
[118]
Alfaras I, Di Germanio C, Bernier M, et al. Pharmacological strategies to retard cardiovascular aging. Circ Res 2016; 118(10): 1626-42.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.307475] [PMID: 27174954]
[119]
Song R. Mechanism of metformin: a tale of two sites. Diabetes Care 2016; 39(2): 187-9.
[http://dx.doi.org/10.2337/dci15-0013] [PMID: 26798149]
[120]
Lv Z, Guo Y. Metformin and its benefits for various diseases. Front Endocrinol (Lausanne) 2020; 11: 191.
[http://dx.doi.org/10.3389/fendo.2020.00191] [PMID: 32425881]
[121]
Valencia WM, Palacio A, Tamariz L, Florez H. Metformin and ageing: improving ageing outcomes beyond glycaemic control. Diabetologia 2017; 60(9): 1630-8.
[http://dx.doi.org/10.1007/s00125-017-4349-5] [PMID: 28770328]
[122]
Anisimov VN, Berstein LM, Egormin PA, et al. Metformin slows down aging and extends life span of female SHR mice. Cell Cycle 2008; 7(17): 2769-73.
[http://dx.doi.org/10.4161/cc.7.17.6625] [PMID: 18728386]
[123]
Martin-Montalvo A, Mercken EM, Mitchell SJ, et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013; 4: 2192.
[http://dx.doi.org/10.1038/ncomms3192] [PMID: 23900241]
[124]
Chen J, Ou Y, Li Y, Hu S, Shao L-W, Liu Y. Metformin extends C. elegans lifespan through lysosomal pathway. eLife 2017; 6: e31268.
[http://dx.doi.org/10.7554/eLife.31268] [PMID: 29027899]
[125]
Mohan M, Al-Talabany S, McKinnie A, et al. A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial. Eur Heart J 2019; 40(41): 3409-17.
[http://dx.doi.org/10.1093/eurheartj/ehz203] [PMID: 30993313]
[126]
Han Y, Xie H, Liu Y, Gao P, Yang X, Shen Z. Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis. Cardiovasc Diabetol 2019; 18(1): 96.
[http://dx.doi.org/10.1186/s12933-019-0900-7] [PMID: 31362743]
[127]
Wang XF, Zhang JY, Li L, Zhao XY, Tao HL, Zhang L. Metformin improves cardiac function in rats via activation of AMP-activated protein kinase. Clin Exp Pharmacol Physiol 2011; 38(2): 94-101.
[http://dx.doi.org/10.1111/j.1440-1681.2010.05470.x] [PMID: 21143620]
[128]
Zhu X, Shen W, Liu Z, et al. Effect of metformin on cardiac metabolism and longevity in aged female mice. Front Cell Dev Biol 2021; 8: 626011.
[http://dx.doi.org/10.3389/fcell.2020.626011] [PMID: 33585467]
[129]
Liu L, Ni YQ, Zhan JK, Liu YS. The role of SGLT2 inhibitors in vascular aging. Aging Dis 2021; 12(5): 1323-36.
[http://dx.doi.org/10.14336/AD.2020.1229] [PMID: 34341711]
[130]
Gorini S, Kim SK, Infante M, et al. Role of aldosterone and mineralocorticoid receptor in cardiovascular aging. Front Endocrinol (Lausanne) 2019; 10: 584.
[http://dx.doi.org/10.3389/fendo.2019.00584] [PMID: 31507534]
[131]
Filippatos G, Anker SD, Agarwal R, et al. FIDELIO-DKD Investigators. Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes. Circulation 2021; 143(6): 540-52.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051898] [PMID: 33198491]
[132]
Grune J, Beyhoff N, Smeir E, et al. Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone’s antifibrotic activity. Hypertension 2018; 71(4): 599-608.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10360] [PMID: 29437893]
[133]
Li J, Zhang C-X, Liu Y-M, Chen K-L, Chen G. A comparative study of anti-aging properties and mechanism: resveratrol and caloric restriction. Oncotarget 2017; 8(39): 65717-29.
[http://dx.doi.org/10.18632/oncotarget.20084] [PMID: 29029466]
[134]
Bhullar KS, Hubbard BP. Lifespan and healthspan extension by resveratrol. Biochim Biophys Acta (BBA) Mol Basis Dis 2015; 1852: 1209-18.
[http://dx.doi.org/10.1016/j.bbadis.2015.01.012]
[135]
Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 2004; 430(7000): 686-9.
[http://dx.doi.org/10.1038/nature02789] [PMID: 15254550]
[136]
Viswanathan M, Kim SK, Berdichevsky A, Guarente L. A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell 2005; 9(5): 605-15.
[http://dx.doi.org/10.1016/j.devcel.2005.09.017] [PMID: 16256736]
[137]
Wang C, Wheeler CT, Alberico T, et al. The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster. Age (Dordr) 2013; 35(1): 69-81.
[http://dx.doi.org/10.1007/s11357-011-9332-3] [PMID: 22083438]
[138]
Rascón B, Hubbard BP, Sinclair DA, Amdam GV. The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. Aging (Albany NY) 2012; 4(7): 499-508.
[http://dx.doi.org/10.18632/aging.100474] [PMID: 22868943]
[139]
da Luz PL, Tanaka L, Brum PC, et al. Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. Atherosclerosis 2012; 224(1): 136-42.
[http://dx.doi.org/10.1016/j.atherosclerosis.2012.06.007] [PMID: 22818625]
[140]
Cencioni C, Spallotta F, Mai A, et al. Sirtuin function in aging heart and vessels. J Mol Cell Cardiol 2015; 83: 55-61.
[http://dx.doi.org/10.1016/j.yjmcc.2014.12.023] [PMID: 25579854]
[141]
Bai B, Vanhoutte PM, Wang Y. Loss-of-SIRT1 function during vascular ageing: hyperphosphorylation mediated by cyclin-dependent kinase 5. Trends Cardiovasc Med 2014; 24(2): 81-4.
[http://dx.doi.org/10.1016/j.tcm.2013.07.001] [PMID: 23968571]
[142]
Bai B, Liang Y, Xu C, et al. Cyclin-dependent kinase 5-mediated hyperphosphorylation of sirtuin-1 contributes to the development of endothelial senescence and atherosclerosis. Circulation 2012; 126(6): 729-40.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.118778] [PMID: 22753194]
[143]
Tanno M, Kuno A, Horio Y, Miura T. Emerging beneficial roles of sirtuins in heart failure. Basic Res Cardiol 2012; 107(4): 273.
[http://dx.doi.org/10.1007/s00395-012-0273-5] [PMID: 22622703]
[144]
Hsu Y-J, Hsu S-C, Hsu C-P, et al. Sirtuin 1 protects the aging heart from contractile dysfunction mediated through the inhibition of endoplasmic reticulum stress-mediated apoptosis in cardiac-specific Sirtuin 1 knockout mouse model. Int J Cardiol 2017; 228: 543-52.
[http://dx.doi.org/10.1016/j.ijcard.2016.11.247] [PMID: 27875732]
[145]
Fujitaka K, Otani H, Jo F, et al. Modified resveratrol Longevinex improves endothelial function in adults with metabolic syndrome receiving standard treatment. Nutr Res 2011; 31(11): 842-7.
[http://dx.doi.org/10.1016/j.nutres.2011.09.028] [PMID: 22118755]
[146]
Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res 2012; 32(7): 537-41.
[http://dx.doi.org/10.1016/j.nutres.2012.06.003] [PMID: 22901562]
[147]
Imamura H, Yamaguchi T, Nagayama D, Saiki A, Shirai K, Tatsuno I. Resveratrol ameliorates arterial stiffness assessed by cardio-ankle vascular index in patients with type 2 diabetes mellitus. Int Heart J 2017; 58(4): 577-83.
[http://dx.doi.org/10.1536/ihj.16-373] [PMID: 28701674]
[148]
Wong RH, Berry NM, Coates AM, et al. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. J Hypertens 2013; 31(9): 1819-27.
[http://dx.doi.org/10.1097/HJH.0b013e328362b9d6] [PMID: 23743811]
[149]
Timmers S, Konings E, Bilet L, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 2011; 14(5): 612-22.
[http://dx.doi.org/10.1016/j.cmet.2011.10.002] [PMID: 22055504]
[150]
Tomé-Carneiro J, Larrosa M, Yáñez-Gascón MJ, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res 2013; 72: 69-82.
[http://dx.doi.org/10.1016/j.phrs.2013.03.011] [PMID: 23557933]
[151]
Dyck GJB, Raj P, Zieroth S, Dyck JRB, Ezekowitz JA. The effects of resveratrol in patients with cardiovascular disease and heart failure: a narrative review. Int J Mol Sci 2019; 20(4): 904.
[http://dx.doi.org/10.3390/ijms20040904] [PMID: 30791450]
[152]
Huang H, Chen G, Liao D, Zhu Y, Pu R, Xue X. The effects of resveratrol intervention on risk markers of cardiovascular health in overweight and obese subjects: a pooled analysis of randomized controlled trials. Obes Rev 2016; 17(12): 1329-40.
[http://dx.doi.org/10.1111/obr.12458] [PMID: 27456934]
[153]
Olesen J, Gliemann L, Biensø R, Schmidt J, Hellsten Y, Pilegaard H. Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men. J Physiol 2014; 592(8): 1873-86.
[http://dx.doi.org/10.1113/jphysiol.2013.270256] [PMID: 24514907]
[154]
Bo S, Ponzo V, Ciccone G, et al. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Pharmacol Res 2016; 111: 896-905.
[http://dx.doi.org/10.1016/j.phrs.2016.08.010] [PMID: 27520400]
[155]
van der Made SM, Plat J, Mensink RP. Resveratrol does not influence metabolic risk markers related to cardiovascular health in overweight and slightly obese subjects: a randomized, placebo- controlled crossover trial. PLoS One 2015; 10(3): e0118393.
[http://dx.doi.org/10.1371/journal.pone.0118393] [PMID: 25790328]
[156]
Yoshino J, Conte C, Fontana L, et al. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab 2012; 16(5): 658-64.
[http://dx.doi.org/10.1016/j.cmet.2012.09.015] [PMID: 23102619]
[157]
Brown NJ, Vaughan DE. Angiotensin-converting enzyme inhibitors. Circulation 1998; 97(14): 1411-20.
[http://dx.doi.org/10.1161/01.CIR.97.14.1411] [PMID: 9577953]
[158]
Blagosklonny MV. Disease or not, aging is easily treatable. Aging (Albany NY) 2018; 10(11): 3067-78.
[http://dx.doi.org/10.18632/aging.101647] [PMID: 30448823]
[159]
Santos EL, de Picoli Souza K, da Silva ED, et al. Long term treatment with ACE inhibitor enalapril decreases body weight gain and increases life span in rats. Biochem Pharmacol 2009; 78(8): 951-8.
[http://dx.doi.org/10.1016/j.bcp.2009.06.018] [PMID: 19549507]
[160]
Spindler SR, Mote PL, Flegal JM. Combined statin and angiotensin-converting enzyme (ACE) inhibitor treatment increases the lifespan of long-lived F1 male mice. Age (Dordr) 2016; 38(5-6): 379-91.
[http://dx.doi.org/10.1007/s11357-016-9948-4] [PMID: 27590905]
[161]
Basso N, Cini R, Pietrelli A, Ferder L, Terragno NA, Inserra F. Protective effect of long-term angiotensin II inhibition. Am J Physiol Heart Circ Physiol 2007; 293(3): H1351-8.
[http://dx.doi.org/10.1152/ajpheart.00393.2007] [PMID: 17557916]
[162]
Gianni M, Bosch J, Pogue J, et al. Effect of long-term ACE-inhibitor therapy in elderly vascular disease patients. Eur Heart J 2007; 28(11): 1382-8.
[http://dx.doi.org/10.1093/eurheartj/ehm017] [PMID: 17395677]
[163]
Inserra F, Romano L, Ercole L, de Cavanagh EM, Ferder L. Cardiovascular changes by long-term inhibition of the renin-angiotensin system in aging. Hypertension 1995; 25(3): 437-42.
[http://dx.doi.org/10.1161/01.HYP.25.3.437] [PMID: 7875769]
[164]
Sakata Y, Yamamoto K, Mano T, et al. Temocapril prevents transition to diastolic heart failure in rats even if initiated after appearance of LV hypertrophy and diastolic dysfunction. Cardiovasc Res 2003; 57(3): 757-65.
[http://dx.doi.org/10.1016/S0008-6363(02)00722-8] [PMID: 12618237]
[165]
Solomon SD, Janardhanan R, Verma A, et al. Valsartan In Diastolic Dysfunction (VALIDD) Investigators. Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet 2007; 369(9579): 2079-87.
[http://dx.doi.org/10.1016/S0140-6736(07)60980-5] [PMID: 17586303]
[166]
Flather MD, Yusuf S, Køber L, et al. ACE-Inhibitor Myocardial Infarction Collaborative Group. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. Lancet 2000; 355(9215): 1575-81.
[http://dx.doi.org/10.1016/S0140-6736(00)02212-1] [PMID: 10821360]
[167]
Beldhuis IE, Streng KW, Ter Maaten JM, et al. Renin–angiotensin system inhibition, worsening renal function, and outcome in heart failure patients with reduced and preserved ejection fraction: a meta-analysis of published study data. Circ Heart Fail 2017; 10(2): e003588.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.116.003588] [PMID: 28209765]
[168]
Fukuta H, Goto T, Wakami K, Kamiya T, Ohte N. Effect of renin-angiotensin system inhibition on cardiac structure and function and exercise capacity in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials. Heart Fail Rev 2020; 1-8.
[PMID: 32562021]
[169]
Cruickshank JM. Are we misunderstanding beta-blockers. Int J Cardiol 2007; 120(1): 10-27.
[http://dx.doi.org/10.1016/j.ijcard.2007.01.069] [PMID: 17433471]
[170]
Raposeiras-Roubín S, Abu-Assi E, Redondo-Diéguez A, et al. Prognostic benefit of beta-blockers after acute coronary syndrome with preserved systolic function. Still relevant today? Rev Esp Cardiol (Engl Ed) 2015; 68(7): 585-91.
[http://dx.doi.org/10.1016/j.rec.2014.07.028] [PMID: 25511558]
[171]
Choo EH, Chang K, Ahn Y, et al. Benefit of β-blocker treatment for patients with acute myocardial infarction and preserved systolic function after percutaneous coronary intervention. Heart 2014; 100(6): 492-9.
[http://dx.doi.org/10.1136/heartjnl-2013-305137] [PMID: 24395980]
[172]
Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998; 339(8): 489-97.
[http://dx.doi.org/10.1056/NEJM199808203390801] [PMID: 9709041]
[173]
Ladage D, Schwinger RH, Brixius K. Cardio-selective beta-blocker: pharmacological evidence and their influence on exercise capacity. Cardiovasc Ther 2013; 31(2): 76-83.
[http://dx.doi.org/10.1111/j.1755-5922.2011.00306.x] [PMID: 22279967]
[174]
Ziff OJ, Samra M, Howard JP, et al. Beta-blocker efficacy across different cardiovascular indications: an umbrella review and meta-analytic assessment. BMC Med 2020; 18(1): 103.
[http://dx.doi.org/10.1186/s12916-020-01564-3] [PMID: 32366251]
[175]
Dondo TB, Hall M, West RM, et al. β-blockers and mortality after acute myocardial infarction in patients without heart failure or ventricular dysfunction. J Am Coll Cardiol 2017; 69(22): 2710-20.
[http://dx.doi.org/10.1016/j.jacc.2017.03.578] [PMID: 28571635]
[176]
Liao Y, Asakura M, Takashima S, et al. Celiprolol, a vasodilatory β-blocker, inhibits pressure overload-induced cardiac hypertrophy and prevents the transition to heart failure via nitric oxide-dependent mechanisms in mice. Circulation 2004; 110(6): 692-9.
[http://dx.doi.org/10.1161/01.CIR.0000137831.08683.E1] [PMID: 15262839]
[177]
Bristow MR. β-adrenergic receptor blockade in chronic heart failure. Circulation 2000; 101(5): 558-69.
[http://dx.doi.org/10.1161/01.CIR.101.5.558] [PMID: 10662755]
[178]
Spindler SR, Mote PL, Li R, et al. β1-Adrenergic receptor blockade extends the life span of Drosophila and long-lived mice. Age (Dordr) 2013; 35(6): 2099-109.
[http://dx.doi.org/10.1007/s11357-012-9498-3] [PMID: 23314750]
[179]
Suojanen L, Haring A, Tikkakoski A, et al. Haemodynamic influences of bisoprolol in hypertensive middle-aged men: a double-blind, randomized, placebo-controlled cross-over study. Basic Clin Pharmacol Toxicol 2017; 121(2): 130-7.
[http://dx.doi.org/10.1111/bcpt.12771] [PMID: 28256104]
[180]
Leosco D, Rengo G, Iaccarino G, et al. Exercise training and β-blocker treatment ameliorate age-dependent impairment of β-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation. Am J Physiol Heart Circ Physiol 2007; 293(3): H1596-603.
[http://dx.doi.org/10.1152/ajpheart.00308.2007] [PMID: 17557919]
[181]
Eijsvogels TM, Molossi S, Lee DC, Emery MS, Thompson PD. Exercise at the extremes: the amount of exercise to reduce cardiovascular events. J Am Coll Cardiol 2016; 67(3): 316-29.
[http://dx.doi.org/10.1016/j.jacc.2015.11.034] [PMID: 26796398]
[182]
Thijssen DH, Maiorana AJ, O’Driscoll G, Cable NT, Hopman MT, Green DJ. Impact of inactivity and exercise on the vasculature in humans. Eur J Appl Physiol 2010; 108(5): 845-75.
[http://dx.doi.org/10.1007/s00421-009-1260-x] [PMID: 19943061]
[183]
Roh JD, Houstis N, Yu A, et al. Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice. Aging Cell 2020; 19(6): e13159.
[http://dx.doi.org/10.1111/acel.13159] [PMID: 32441410]
[184]
Beaumont A, Campbell A, Grace F, Sculthorpe N. Cardiac response to exercise in normal ageing: what can we learn from masters athletes? Curr Cardiol Rev 2018; 14(4): 245-53.
[http://dx.doi.org/10.2174/1573403X14666180810155513] [PMID: 30095058]
[185]
Leosco D, Parisi V, Femminella GD, et al. Effects of exercise training on cardiovascular adrenergic system. Front Physiol 2013; 4: 348.
[http://dx.doi.org/10.3389/fphys.2013.00348] [PMID: 24348425]
[186]
Jakovljevic DG. Physical activity and cardiovascular aging: Physiological and molecular insights. Exp Gerontol 2018; 109: 67-74.
[http://dx.doi.org/10.1016/j.exger.2017.05.016] [PMID: 28546086]
[187]
Pinckard K, Baskin KK, Stanford KI. Effects of exercise to improve cardiovascular health. Front Cardiovasc Med 2019; 6: 69.
[http://dx.doi.org/10.3389/fcvm.2019.00069] [PMID: 31214598]
[188]
Stratton JR, Levy WC, Cerqueira MD, Schwartz RS, Abrass IB. Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men. Circulation 1994; 89(4): 1648-55.
[http://dx.doi.org/10.1161/01.CIR.89.4.1648] [PMID: 8149532]
[189]
Scarpace PJ, Shu Y, Tümer N. Influence of exercise training on myocardial beta-adrenergic signal transduction: differential regulation with age. J Appl Physiol 1994; 77(2): 737-41.
[http://dx.doi.org/10.1152/jappl.1994.77.2.737] [PMID: 8002522]
[190]
Høydal MA, Stølen TO, Kettlewell S, et al. Exercise training reverses myocardial dysfunction induced by CaMKIIδC overexpression by restoring Ca2+ homeostasis. J Appl Physiol 2016; 121(1): 212-20.
[http://dx.doi.org/10.1152/japplphysiol.00188.2016] [PMID: 27231311]
[191]
Böhm M, Dorner H, Htun P, Lensche H, Platt D, Erdmann E. Effects of exercise on myocardial adenylate cyclase and Gi alpha expression in senescence. Am J Physiol 1993; 264(3 Pt 2): H805-14.
[PMID: 8384423]
[192]
Leosco D, Rengo G, Iaccarino G, et al. Exercise training and-blocker treatment ameliorate age-dependent impairment of-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation. Cardiovasc Res 2008; 78: 385-94.
[http://dx.doi.org/10.1093/cvr/cvm109] [PMID: 18093988]
[193]
Tate CA, Helgason T, Hyek MF, et al. SERCA2a and mitochondrial cytochrome oxidase expression are increased in hearts of exercise-trained old rats. Am J Physiol 1996; 271(1 Pt 2): H68-72.
[PMID: 8760159]
[194]
Thomas MM, Vigna C, Betik AC, Tupling AR, Hepple RT. Cardiac calcium pump inactivation and nitrosylation in senescent rat myocardium are not attenuated by long-term treadmill training. Exp Gerontol 2011; 46(10): 803-10.
[http://dx.doi.org/10.1016/j.exger.2011.06.005] [PMID: 21763413]
[195]
Iemitsu M, Miyauchi T, Maeda S, et al. Exercise training improves cardiac function-related gene levels through thyroid hormone receptor signaling in aged rats. Am J Physiol Heart Circ Physiol 2004; 286(5): H1696-705.
[http://dx.doi.org/10.1152/ajpheart.00761.2003] [PMID: 14704232]
[196]
Walton RD, Jones SA, Rostron KA, et al. Interactions of short-term and chronic treadmill training with aging of the left ventricle of the heart. J Gerontol Series A: Biomed Sci Med Sci 2016; 71(8): 1005-13.
[http://dx.doi.org/10.1093/gerona/glv093] [PMID: 26248561]
[197]
Spina RJ, Turner MJ, Ehsani AA. β-adrenergic-mediated improvement in left ventricular function by exercise training in older men. Am J Physiol 1998; 274(2): H397-404.
[PMID: 9486240]
[198]
Stewart KJ, Bacher AC, Turner KL, et al. Effect of exercise on blood pressure in older persons: a randomized controlled trial. Arch Intern Med 2005; 165(7): 756-62.
[http://dx.doi.org/10.1001/archinte.165.7.756] [PMID: 15824294]
[199]
Tanaka H. Antiaging effects of aerobic exercise on systemic arteries. Hypertension 2019; 74: A11913179.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13179] [PMID: 31256721]
[200]
Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR. Aging, habitual exercise, and dynamic arterial compliance. Circulation 2000; 102(11): 1270-5.
[http://dx.doi.org/10.1161/01.CIR.102.11.1270] [PMID: 10982542]
[201]
Sugawara J, Komine H, Hayashi K, et al. Systemic α-adrenergic and nitric oxide inhibition on basal limb blood flow: effects of endurance training in middle-aged and older adults. Am J Physiol Heart Circ Physiol 2007; 293(3): H1466-72.
[http://dx.doi.org/10.1152/ajpheart.00273.2007] [PMID: 17496216]
[202]
Thijssen DH, Rongen GA, van Dijk A, Smits P, Hopman MT. Enhanced endothelin-1-mediated leg vascular tone in healthy older subjects. J Appl Physiol 2007; 103(3): 852-7.
[http://dx.doi.org/10.1152/japplphysiol.00357.2007] [PMID: 17556493]
[203]
Van Guilder GP, Westby CM, Greiner JJ, Stauffer BL, DeSouza CA. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise. Hypertension 2007; 50(2): 403-9.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.088294] [PMID: 17576858]
[204]
Brandon LJ, Sharon BF, Boyette LW. Effects of a four-month strength training program on blood pressure in older adults. J Nutr Health Aging 1997; 1(2): 98-102.
[PMID: 16491533]
[205]
Ben-Sira D, Oliveira J. Hypertension in aging: physical activity as primary prevention. Eur Rev Aging Phys Act 2007; 4: 85-9.
[http://dx.doi.org/10.1007/s11556-007-0023-0]
[206]
Tanaka H, Dinenno FA, Seals DR. Reductions in central arterial compliance with age are related to sympathetic vasoconstrictor nerve activity in healthy men. Hypertens Res 2017; 40(5): 493-5.
[http://dx.doi.org/10.1038/hr.2016.182] [PMID: 28100923]
[207]
Campbell A, Grace F, Ritchie L, Beaumont A, Sculthorpe N. Long-term aerobic exercise improves vascular function into old age: a systematic review, meta-analysis and meta regression of observational and interventional studies. Front Physiol 2019; 10: 31.
[http://dx.doi.org/10.3389/fphys.2019.00031] [PMID: 30863313]
[208]
DeSouza CA, Shapiro LF, Clevenger CM, et al. Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation 2000; 102(12): 1351-7.
[http://dx.doi.org/10.1161/01.CIR.102.12.1351] [PMID: 10993851]
[209]
Taddei S, Galetta F, Virdis A, et al. Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation 2000; 101(25): 2896-901.
[http://dx.doi.org/10.1161/01.CIR.101.25.2896] [PMID: 10869260]
[210]
Spier SA, Delp MD, Meininger CJ, Donato AJ, Ramsey MW, Muller-Delp JM. Effects of ageing and exercise training on endothelium-dependent vasodilatation and structure of rat skeletal muscle arterioles. J Physiol 2004; 556(Pt 3): 947-58.
[http://dx.doi.org/10.1113/jphysiol.2003.060301] [PMID: 15004211]
[211]
Moreau KL, Gavin KM, Plum AE, Seals DR. Ascorbic acid selectively improves large elastic artery compliance in postmenopausal women. Hypertension 2005; 45(6): 1107-12.
[http://dx.doi.org/10.1161/01.HYP.0000165678.63373.8c] [PMID: 15867135]
[212]
Seals DR, Desouza CA, Donato AJ, Tanaka H. Habitual exercise and arterial aging. J Appl Physiol 2008; 105(4): 1323-32.
[http://dx.doi.org/10.1152/japplphysiol.90553.2008] [PMID: 18583377]
[213]
Moreau KL, Donato AJ, Seals DR, et al. Arterial intima-media thickness: site-specific associations with HRT and habitual exercise. Am J Physiol Heart Circ Physiol 2002; 283(4): H1409-17.
[http://dx.doi.org/10.1152/ajpheart.00035.2002] [PMID: 12234791]
[214]
Tanaka H, Seals DR, Monahan KD, Clevenger CM, DeSouza CA, Dinenno FA. Regular aerobic exercise and the age-related increase in carotid artery intima-media thickness in healthy men. J Appl Physiol 2002; 92(4): 1458-64.
[http://dx.doi.org/10.1152/japplphysiol.00824.2001] [PMID: 11896010]
[215]
Donato AJ, Lesniewski LA, Delp MD. Ageing and exercise training alter adrenergic vasomotor responses of rat skeletal muscle arterioles. J Physiol 2007; 579(Pt 1): 115-25.
[http://dx.doi.org/10.1113/jphysiol.2006.120055] [PMID: 17082231]
[216]
Spina RJ, Bourey RE, Ogawa T, Ehsani AA. Effects of exercise training on α-adrenergic mediated pressor responses and baroreflex function in older subjects. J Gerontol 1994; 49(6): B277-81.
[http://dx.doi.org/10.1093/geronj/49.6.B277] [PMID: 7963274]
[217]
Silva AS, Zanesco A. Physical exercise, ß-adrenergic receptors, and vascular. J Vasc Bras 2010; 9(2): 47-56.
[218]
Leosco D, Iaccarino G, Cipolletta E, et al. Exercise restores β-adrenergic vasorelaxation in aged rat carotid arteries. Am J Physiol Heart Circ Physiol 2003; 285(1): H369-74.
[http://dx.doi.org/10.1152/ajpheart.00019.2003] [PMID: 12637361]
[219]
Cadeddu C, Nocco S, Cugusi L, et al. Effects of metformin and exercise training, alone or in combination, on cardiac function in individuals with insulin resistance. Cardiol Ther 2016; 5(1): 63-73.
[http://dx.doi.org/10.1007/s40119-016-0057-3] [PMID: 26831122]
[220]
Cadeddu C, Nocco S, Cugusi L, et al. Effects of metformin and exercise training, alone or in association, on cardio-pulmonary performance and quality of life in insulin resistance patients. Cardiovasc Diabetol 2014; 13: 93.
[http://dx.doi.org/10.1186/1475-2840-13-93] [PMID: 24884495]
[221]
Viskochil R, Malin SK, Blankenship JM, Braun B. Exercise training and metformin, but not exercise training alone, decreases insulin production and increases insulin clearance in adults with prediabetes. J Appl Physiol 2017; 123(1): 243-8.
[http://dx.doi.org/10.1152/japplphysiol.00790.2016] [PMID: 28473613]
[222]
Linden MA, Fletcher JA, Morris EM, et al. Combining metformin and aerobic exercise training in the treatment of type 2 diabetes and NAFLD in OLETF rats. Am J Physiol Endocrinol Metab 2014; 306(3): E300-10.
[http://dx.doi.org/10.1152/ajpendo.00427.2013] [PMID: 24326426]
[223]
Malin SK, Nightingale J, Choi SE, Chipkin SR, Braun B. Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults. Obesity (Silver Spring) 2013; 21(1): 93-100.
[http://dx.doi.org/10.1002/oby.20235] [PMID: 23505172]
[224]
Konopka AR, Laurin JL, Schoenberg HM, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell 2019; 18(1): e12880.
[http://dx.doi.org/10.1111/acel.12880] [PMID: 30548390]
[225]
Malin SK, Braun B. Impact of metformin on exercise-induced metabolic adaptations to lower type 2 diabetes risk. Exerc Sport Sci Rev 2016; 44(1): 4-11.
[http://dx.doi.org/10.1249/JES.0000000000000070] [PMID: 26583801]
[226]
Gliemann L, Schmidt JF, Olesen J, et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol 2013; 591(20): 5047-59.
[http://dx.doi.org/10.1113/jphysiol.2013.258061] [PMID: 23878368]
[227]
Gliemann L, Nyberg M, Hellsten Y. Effects of exercise training and resveratrol on vascular health in aging. Free Radic Biol Med 2016; 98: 165-76.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.03.037] [PMID: 27085843]
[228]
Gliemann L, Olesen J, Biensø RS, et al. Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men. Am J Physiol Heart Circ Physiol 2014; 307(8): H1111-9.
[http://dx.doi.org/10.1152/ajpheart.00168.2014] [PMID: 25128170]
[229]
Buford TW, Anton SD. Resveratrol as a supplement to exercise training: friend or foe? J Physiol 2014; 592(3): 551-2.
[http://dx.doi.org/10.1113/jphysiol.2013.267922] [PMID: 24488074]
[230]
Smoliga JM, Blanchard OL. Recent data do not provide evidence that resveratrol causes ‘mainly negative’ or ‘adverse’ effects on exercise training in humans. J Physiol 2013; 591(20): 5251-2.
[http://dx.doi.org/10.1113/jphysiol.2013.262956] [PMID: 24130323]
[231]
Dolinsky VW, Jones KE, Sidhu RS, et al. Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats. J Physiol 2012; 590(11): 2783-99.
[http://dx.doi.org/10.1113/jphysiol.2012.230490] [PMID: 22473781]
[232]
Kan N-W, Ho C-S, Chiu Y-S, et al. Effects of resveratrol supplementation and exercise training on exercise performance in middle-aged mice. Molecules 2016; 21(5): 661.
[http://dx.doi.org/10.3390/molecules21050661] [PMID: 27213310]
[233]
Alway SE, McCrory JL, Kearcher K, et al. Resveratrol enhances exercise-induced cellular and functional adaptations of skeletal muscle in older men and women. J Gerontol Series A: Biomed Sci Med Sci 2017; 72(12): 1595-606.
[http://dx.doi.org/10.1093/gerona/glx089] [PMID: 28505227]
[234]
Lin C-H, Lin C-C, Ting W-J, et al. Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts. Age (Dordr) 2014; 36(5): 9705.
[http://dx.doi.org/10.1007/s11357-014-9705-5] [PMID: 25158994]
[235]
Muhammad MH, Allam MM. Resveratrol and/or exercise training counteract aging-associated decline of physical endurance in aged mice; targeting mitochondrial biogenesis and function. J Physiol Sci 2018; 68(5): 681-8.
[http://dx.doi.org/10.1007/s12576-017-0582-4] [PMID: 29230719]
[236]
Ziada AM. Additional salutary effects of the combination of exercise training and an angiotensin-converting enzyme inhibitor on the left ventricular function of spontaneously hypertensive rats. J Hypertens 2009; 27(6): 1309-16.
[http://dx.doi.org/10.1097/HJH.0b013e328329fb55] [PMID: 19462500]
[237]
Kinoshita M, Nakaya Y, Harada N, Takahashi A, Nomura M, Bando S. Combination therapy of exercise and angiotensin-converting enzyme inhibitor markedly improves insulin sensitivities in hypertensive patients with insulin resistance. Circ J 2002; 66(7): 655-8.
[http://dx.doi.org/10.1253/circj.66.655] [PMID: 12135133]
[238]
Ziada AM, Hassan MO, Tahlilkar KI, Inuwa IM. Long-term exercise training and angiotensin-converting enzyme inhibition differentially enhance myocardial capillarization in the spontaneously hypertensive rat. J Hypertens 2005; 23(6): 1233-40.
[http://dx.doi.org/10.1097/01.hjh.0000170387.61579.ab] [PMID: 15894900]
[239]
Steen MS, Foianini KR, Youngblood EB, Kinnick TR, Jacob S, Henriksen EJ. Interactions of exercise training and ACE inhibition on insulin action in obese Zucker rats. J Appl Physiol 1999; 86(6): 2044-51.
[http://dx.doi.org/10.1152/jappl.1999.86.6.2044] [PMID: 10368372]
[240]
Xu X, Wan W, Ji L, et al. Exercise training combined with angiotensin II receptor blockade limits post-infarct ventricular remodelling in rats. Cardiovasc Res 2008; 78(3): 523-32.
[http://dx.doi.org/10.1093/cvr/cvn028] [PMID: 18252761]
[241]
Sumukadas D, Band M, Miller S, et al. Do ACE inhibitors improve the response to exercise training in functionally impaired older adults? A randomized controlled trial. J Gerontol Series A: Biomed Sci Med Sci 2014; 69(6): 736-43.
[http://dx.doi.org/10.1093/gerona/glt142] [PMID: 24201696]
[242]
Guo Q, Minami N, Mori N, et al. Effects of estradiol, angiotensin-converting enzyme inhibitor and exercise training on exercise capacity and skeletal muscle in old female rats. Clin Exp Hypertens 2010; 32(2): 76-83.
[http://dx.doi.org/10.3109/10641960902993046] [PMID: 20374181]
[243]
Nishi I, Noguchi T, Iwanaga Y, et al. Effects of exercise training in patients with chronic heart failure and advanced left ventricular systolic dysfunction receiving β-blockers. Circ J 2011; 75(7): 1649-55.
[http://dx.doi.org/10.1253/circj.CJ-10-0899] [PMID: 21613745]
[244]
Medeiros WM, de Luca FA, de Figueredo Júnior AR, Mendes FAR, Gun C. Heart rate recovery improvement in patients following acute myocardial infarction: exercise training, β-blocker therapy or both. Clin Physiol Funct Imaging 2018; 38(3): 351-9.
[http://dx.doi.org/10.1111/cpf.12420] [PMID: 28402023]
[245]
Dunkley JC, Irion CI, Yousefi K, et al. Carvedilol and exercise combination therapy improves systolic but not diastolic function and reduces plasma osteopontin in Col4a3-/- Alport mice. Am J Physiol Heart Circ Physiol 2021; 320(5): H1862-72.
[http://dx.doi.org/10.1152/ajpheart.00535.2020] [PMID: 33769915]
[246]
Vanzelli AS, Medeiros A, Rolim N, et al. Integrative effect of carvedilol and aerobic exercise training therapies on improving cardiac contractility and remodeling in heart failure mice. PLoS One 2013; 8(5): e62452.
[http://dx.doi.org/10.1371/journal.pone.0062452] [PMID: 23658728]
[247]
Minami N, Yoshikawa T, Kataoka H, et al. Effects of exercise and β-blocker on blood pressure and baroreflexes in spontaneously hypertensive rats. Am J Hypertens 2003; 16(11 Pt 1): 966-72.
[http://dx.doi.org/10.1016/S0895-7061(03)01010-0] [PMID: 14573336]