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Blood pressure, antihypertensive drugs, and incident frailty: The Multidomain Alzheimer Preventive Trial (MAPT)

      Highlights

      • Low blood pressure was associated with a 40% increase in the risk of frailty.
      • Participants with low blood pressure and those on two or more antihypertensive drugs were at the greatest risk of frailty.
      • Low blood pressure could be a new marker for identifying older adults at higher risk of frailty.

      Abstract

      Objectives

      To examine the association of (1) high and low blood pressure (BP) and (2) antihypertensive (AH) drug use with incident frailty.

      Study design

      We conducted a secondary analysis of data from the Multidomain Alzheimer Preventive Trial (MAPT), in which 1394 non-frail community-dwelling participants aged ≥70 years were followed up for 5 years. BP was measured once at baseline in a lying position using a validated electronic device. High BP was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg, and low BP as systolic BP ≤ 110 mm Hg and/or diastolic BP ≤ 70 mm Hg. AH drugs were assessed at baseline and classified according to the Anatomical Therapeutic Chemical (ATC) code.

      Main outcome measures

      Incident frailty over the 5 years was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses.

      Results

      Low BP was associated with a greater risk of frailty (HR = 1.43, 95% CI [1.07–1.92], p = 0.02) after adjustment for age, sex, education, AH drug use, BMI, diabetes, ischemic heart disease, congestive heart failure, AF, stroke, MAPT randomization group, sit-to-stand chair test and pre-frailty. Participants with low BP and those on two or more AH drugs were at the greatest risk of frailty. Neither high BP (HR = 0.84, 95% CI [0.63–1.22], p = 0.24) nor AH drug use (HR = 1.21, 95% CI [0.89–1.64], p = 0.22) was independently associated with incident frailty.

      Conclusions

      Low BP could be used as a new marker for identifying older adults at higher risk of frailty.
      Clinicaltrials.gov registration number: NCT00672685.

      Keywords

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      References

        • Clegg A.
        • Young J.
        • Iliffe S.
        • Rikkert M.O.
        • Rockwood K.
        Frailty in elderly people.
        Lancet Lond. Engl. 2013; 381: 752-762https://doi.org/10.1016/S0140-6736(12)62167-9
        • Afilalo J.
        • Alexander K.P.
        • Mack M.J.
        • Maurer M.S.
        • Green P.
        • Allen L.A.
        • Popma J.J.
        • Ferrucci L.
        • Forman D.E.
        Frailty assessment in the cardiovascular care of older adults.
        J. Am. Coll. Cardiol. 2014; 63: 747-762https://doi.org/10.1016/j.jacc.2013.09.070
        • Onder G.
        • Vetrano D.L.
        • Marengoni A.
        • Bell J.S.
        • Johnell K.
        • Palmer K.
        Optimising Pharmacotherapy through Pharmacoepidemiology Network (OPPEN), accounting for frailty when treating chronic diseases.
        Eur. J. Intern. Med. 2018; 56: 49-52https://doi.org/10.1016/j.ejim.2018.02.021
        • Cho C.Y.
        • Alessi C.A.
        • Cho M.
        • Aronow H.U.
        • Stuck A.E.
        • Rubenstein L.Z.
        • Beck J.C.
        The association between chronic illness and functional change among participants in a comprehensive geriatric assessment program.
        J. Am. Geriatr. Soc. 1998; 46: 677-682https://doi.org/10.1111/j.1532-5415.1998.tb03800.x
        • Afilalo J.
        • Karunananthan S.
        • Eisenberg M.J.
        • Alexander K.P.
        • Bergman H.
        Role of frailty in patients with cardiovascular disease.
        Am. J. Cardiol. 2009; 103: 1616-1621https://doi.org/10.1016/j.amjcard.2009.01.375
        • Vetrano D.L.
        • Palmer K.M.
        • Galluzzo L.
        • Giampaoli S.
        • Marengoni A.
        • Bernabei R.
        • Onder G.
        • Joint Action ADVANTAGE WP4 Group
        Hypertension and frailty: a systematic review and meta-analysis.
        BMJ Open. 2018; 8e024406https://doi.org/10.1136/bmjopen-2018-024406
        • Doba N.
        • Tokuda Y.
        • Goldstein N.E.
        • Kushiro T.
        • Hinohara S.
        A pilot trial to predict frailty syndrome: the Japanese Health Research Volunteer Study.
        Exp. Gerontol. 2012; 47: 638-643https://doi.org/10.1016/j.exger.2012.05.016
        • Castrejón-Pérez R.C.
        • Jiménez-Corona A.
        • Bernabé E.
        • Villa-Romero A.R.
        • Arrivé E.
        • Dartigues J.-F.
        • Gutiérrez-Robledo L.M.
        • Borges-Yáñez S.A.
        Oral disease and 3-year incidence of frailty in Mexican older adults.
        J. Gerontol. A Biol. Sci. Med. Sci. 2017; 72: 951-957https://doi.org/10.1093/gerona/glw201
        • Bouillon K.
        • Kivimäki M.
        • Hamer M.
        • Shipley M.J.
        • Akbaraly T.N.
        • Tabak A.
        • Singh-Manoux A.
        • Batty G.D.
        Diabetes risk factors, diabetes risk algorithms, and the prediction of future frailty: the Whitehall II prospective cohort study.
        J. Am. Med. Dir. Assoc. 2013; 14: e1-e6https://doi.org/10.1016/j.jamda.2013.08.016
        • Barzilay J.I.
        • Blaum C.
        • Moore T.
        • Xue Q.L.
        • Hirsch C.H.
        • Walston J.D.
        • Fried L.P.
        Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study.
        Arch. Intern. Med. 2007; 167: 635-641https://doi.org/10.1001/archinte.167.7.635
        • Odden M.C.
        • Beilby P.R.
        • Peralta C.A.
        Blood pressure in older adults: the importance of frailty.
        Curr. Hypertens. Rep. 2015; 17: 55https://doi.org/10.1007/s11906-015-0564-y
        • Onder G.
        • Penninx B.W.J.H.
        • Balkrishnan R.
        • Fried L.P.
        • Chaves P.H.M.
        • Williamson J.
        • Carter C.
        • Di Bari M.
        • Guralnik J.M.
        • Pahor M.
        Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study.
        Lancet Lond. Engl. 2002; 359: 926-930https://doi.org/10.1016/s0140-6736(02)08024-8
        • Carter C.S.
        • Onder G.
        • Kritchevsky S.B.
        • Pahor M.
        Angiotensin-converting enzyme inhibition intervention in elderly persons: effects on body composition and physical performance.
        J. Gerontol. A Biol. Sci. Med. Sci. 2005; 60: 1437-1446https://doi.org/10.1093/gerona/60.11.1437
        • Andrieu S.
        • Guyonnet S.
        • Coley N.
        • Cantet C.
        • Bonnefoy M.
        • Bordes S.
        • Bories L.
        • Cufi M.-N.
        • Dantoine T.
        • Dartigues J.-F.
        • Desclaux F.
        • Gabelle A.
        • Gasnier Y.
        • Pesce A.
        • Sudres K.
        • Touchon J.
        • Robert P.
        • Rouaud O.
        • Legrand P.
        • Payoux P.
        • Caubere J.-P.
        • Weiner M.
        • Carrié I.
        • Ousset P.-J.
        • Vellas B.
        • MAPT Study Group
        Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.
        Lancet Neurol. 2017; 16: 377-389https://doi.org/10.1016/S1474-4422(17)30040-6
        • Vellas B.
        • Carrie I.
        • Gillette-Guyonnet S.
        • Touchon J.
        • Dantoine T.
        • Dartigues J.F.
        • Cuffi M.N.
        • Bordes S.
        • Gasnier Y.
        • Robert P.
        • Bories L.
        • Rouaud O.
        • Desclaux F.
        • Sudres K.
        • Bonnefoy M.
        • Pesce A.
        • Dufouil C.
        • Lehericy S.
        • Chupin M.
        • Mangin J.F.
        • Payoux P.
        • Adel D.
        • Legrand P.
        • Catheline D.
        • Kanony C.
        • Zaim M.
        • Molinier L.
        • Costa N.
        • Delrieu J.
        • Voisin T.
        • Faisant C.
        • Lala F.
        • Nourhashémi F.
        • Rolland Y.
        • Van Kan G.A.
        • Dupuy C.
        • Cantet C.
        • Cestac P.
        • Belleville S.
        • Willis S.
        • Cesari M.
        • Weiner M.W.
        • Soto M.E.
        • Ousset P.J.
        • Andrieu S.
        MAPT study: a multidomain approach for preventing Alzheimer's disease: design and baseline data.
        J. Prev. Alzheimers Dis. 2014; 1: 13-22
        • Lawton M.P.
        Scales to measure competence in everyday activities.
        Psychopharmacol. Bull. 1988; 24: 609-614
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician.
        J. Psychiatr. Res. 1975; 12: 189-198https://doi.org/10.1016/0022-3956(75)90026-6
        • Katz S.
        • Ford A.B.
        • Moskowitz R.W.
        • Jackson B.A.
        • Jaffe M.W.
        Studies of illness in the aged.The index of ADL: a standardized measure of biological and psychosocial function.
        JAMA. 1963; 185: 914-919https://doi.org/10.1001/jama.1963.03060120024016
        • Williams B.
        • Mancia G.
        • Spiering W.
        • Rosei E.Agabiti
        • Azizi M.
        • Burnier M.
        • Clement D.L.
        • Coca A.
        • de Simone G.
        • Dominiczak A.
        • Kahan T.
        • Mahfoud F.
        • Redon J.
        • Ruilope L.
        • Zanchetti A.
        • Kerins M.
        • Kjeldsen S.E.
        • Kreutz R.
        • Laurent S.
        • Lip G.Y.H.
        • McManus R.
        • Narkiewicz K.
        • Ruschitzka F.
        • Schmieder R.E.
        • Shlyakhto E.
        • Tsioufis C.
        • Aboyans V.
        • Desormais I.
        • ESC Scientific Document Group
        2018 ESC/ESH guidelines for the management of arterial hypertension.
        Eur. Heart J. 2018; 39: 3021-3104https://doi.org/10.1093/eurheartj/ehy339
        • Unger T.
        • Borghi C.
        • Charchar F.
        • Khan N.A.
        • Poulter N.R.
        • Prabhakaran D.
        • Ramirez A.
        • Schlaich M.
        • Stergiou G.S.
        • Tomaszewski M.
        • Wainford R.D.
        • Williams B.
        • Schutte A.E.
        International Society of Hypertension global hypertension practice guidelines.
        J. Hypertens. 2020; 38: 982-1004https://doi.org/10.1097/HJH.0000000000002453
        • Ravindrarajah R.
        • Hazra N.C.
        • Hamada S.
        • Charlton J.
        • Jackson S.H.D.
        • Dregan A.
        • Gulliford M.C.
        Systolic blood pressure trajectory, frailty, and all-cause mortality >80 years of age: cohort study using electronic health records.
        Circulation. 2017; 135: 2357-2368https://doi.org/10.1161/CIRCULATIONAHA.116.026687
        • Bangalore S.
        • Qin J.
        • Sloan S.
        • Murphy S.A.
        • Cannon C.P.
        • PROVE IT-TIMI 22 Trial Investigators
        What is the optimal blood pressure in patients after acute coronary syndromes?: Relationship of blood pressure and cardiovascular events in the PRavastatin OR atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial.
        Circulation. 2010; 122: 2142-2151https://doi.org/10.1161/CIRCULATIONAHA.109.905687
        • Bogaerts J.M.K.
        • von Ballmoos L.M.
        • Achterberg W.P.
        • Gussekloo J.
        • Streit S.
        • van der Ploeg M.A.
        • Drewes Y.M.
        • Poortvliet R.K.E.
        Do we AGREE on the targets of antihypertensive drug treatment in older adults: a systematic review of guidelines on primary prevention of cardiovascular diseases.
        Age Ageing. 2022; 51afab192https://doi.org/10.1093/ageing/afab192
        • Masoli J.A.H.
        • Sheppard J.P.
        • Rajkumar C.
        Hypertension management in older patients-are the guideline blood pressure targets appropriate?.
        Age Ageing. 2022; 51afab226https://doi.org/10.1093/ageing/afab226
        • Supiano M.A.
        • Pajewski N.M.
        • Williamson J.D.
        Systolic blood pressure and mortality: role of reverse causation.
        J. Am. Geriatr. Soc. 2018; 66: 205-206https://doi.org/10.1111/jgs.15146
        • Wu C.
        • Smit E.
        • Peralta C.A.
        • Sarathy H.
        • Odden M.C.
        Functional status modifies the association of blood pressure with death in elders: health and retirement study.
        J. Am. Geriatr. Soc. 2017; 65: 1482-1489https://doi.org/10.1111/jgs.14816
        • Shih C.-J.
        • Chen Y.-T.
        • Ou S.-M.
        • Lin C.-H.
        • Tarng D.-C.
        • Taiwan Geriatric Kidney Disease (TGKD) Research Group
        Observed blood pressure and mortality among people aged 65 years and older: a community-based cohort study.
        J. Am. Med. Dir. Assoc. 2016; 17: 654-662https://doi.org/10.1016/j.jamda.2016.04.005
        • Sim J.J.
        • Zhou H.
        • Bhandari S.
        • Wei R.
        • Brettler J.W.
        • Tran-Nguyen J.
        • Handler J.
        • Shimbo D.
        • Jacobsen S.J.
        • Reynolds K.
        Low systolic blood pressure from treatment and association with serious falls/syncope.
        Am. J. Prev. Med. 2018; 55: 488-496https://doi.org/10.1016/j.amepre.2018.05.026
        • Vamos E.P.
        • Harris M.
        • Millett C.
        • Pape U.J.
        • Khunti K.
        • Curcin V.
        • Molokhia M.
        • Majeed A.
        Association of systolic and diastolic blood pressure and all cause mortality in people with newly diagnosed type 2 diabetes: retrospective cohort study.
        BMJ. 2012; 345e5567https://doi.org/10.1136/bmj.e5567
        • Fried L.P.
        • Tangen C.M.
        • Walston J.
        • Newman A.B.
        • Hirsch C.
        • Gottdiener J.
        • Seeman T.
        • Tracy R.
        • Kop W.J.
        • Burke G.
        • McBurnie M.A.
        • Cardiovascular Health Study Collaborative Research Group
        Frailty in older adults: evidence for a phenotype.
        J. Gerontol. A. Biol. Sci. Med. Sci. 2001; 56: M146-M156https://doi.org/10.1093/gerona/56.3.m146
        • Radloff L.S.
        The CES-D scale: a self-report depression scale for research in the general population.
        Appl. Psychol. Meas. 1977; 1: 385-401
        • Gijón-Conde T.
        • Graciani A.
        • López-García E.
        • García-Esquinas E.
        • Laclaustra M.
        • Ruilope L.M.
        • Rodríguez-Artalejo F.
        • Banegas J.R.
        Frailty, disability, and ambulatory blood pressure in older adults.
        J. Am. Med. Dir. Assoc. 2018; 19: 433-438https://doi.org/10.1016/j.jamda.2017.11.014
        • Anker D.
        • Santos-Eggimann B.
        • Zwahlen M.
        • Santschi V.
        • Rodondi N.
        • Wolfson C.
        • Chiolero A.
        Blood pressure in relation to frailty in older adults: a population-based study.
        J. Clin. Hypertens. Greenwich Conn. 2019; 21: 1895-1904https://doi.org/10.1111/jch.13722
        • Benetos A.
        • Labat C.
        • Rossignol P.
        • Fay R.
        • Rolland Y.
        • Valbusa F.
        • Salvi P.
        • Zamboni M.
        • Manckoundia P.
        • Hanon O.
        • Gautier S.
        Treatment with multiple blood pressure medications, achieved blood pressure, and mortality in older nursing home residents: the PARTAGE study.
        JAMA Intern. Med. 2015; 175: 989-995https://doi.org/10.1001/jamainternmed.2014.8012
        • Williamson J.D.
        • Supiano M.A.
        • Applegate W.B.
        • Berlowitz D.R.
        • Campbell R.C.
        • Chertow G.M.
        • Fine L.J.
        • Haley W.E.
        • Hawfield A.T.
        • Ix J.H.
        • Kitzman D.W.
        • Kostis J.B.
        • Krousel-Wood M.A.
        • Launer L.J.
        • Oparil S.
        • Rodriguez C.J.
        • Roumie C.L.
        • Shorr R.I.
        • Sink K.M.
        • Wadley V.G.
        • Whelton P.K.
        • Whittle J.
        • Woolard N.F.
        • Wright J.T.
        • Pajewski N.M.
        • SPRINT Research Group
        Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial.
        JAMA. 2016; 315: 2673-2682https://doi.org/10.1001/jama.2016.7050
        • Sheppard J.P.
        • Mant J.
        • McManus R.J.
        Deprescribing antihypertensive medication in elderly adults-reply.
        JAMA. 2020; 324: 1682-1683https://doi.org/10.1001/jama.2020.16441
        • Pajewski N.M.
        • Berlowitz D.R.
        • Bress A.P.
        • Callahan K.E.
        • Cheung A.K.
        • Fine L.J.
        • Gaussoin S.A.
        • Johnson K.C.
        • King J.
        • Kitzman D.W.
        • Kostis J.B.
        • Lerner A.J.
        • Lewis C.E.
        • Oparil S.
        • Rahman M.
        • Reboussin D.M.
        • Rocco M.V.
        • Snyder J.K.
        • Still C.
        • Supiano M.A.
        • Wadley V.G.
        • Whelton P.K.
        • Wright J.T.
        • Williamson J.D.
        Intensive vs standard blood pressure control in adults 80 years or older: a secondary analysis of the systolic blood pressure intervention trial.
        J. Am. Geriatr. Soc. 2020; 68: 496-504https://doi.org/10.1111/jgs.16272
        • Warwick J.
        • Falaschetti E.
        • Rockwood K.
        • Mitnitski A.
        • Thijs L.
        • Beckett N.
        • Bulpitt C.
        • Peters R.
        No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over.
        BMC Med. 2015; 13: 78https://doi.org/10.1186/s12916-015-0328-1
        • Masoli J.A.H.
        • Delgado J.
        • Pilling L.
        • Strain D.
        • Melzer D.
        Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality.
        Age Ageing. 2020; 49: 807-813https://doi.org/10.1093/ageing/afaa028
        • Whelton P.K.
        • Carey R.M.
        • Aronow W.S.
        • Casey D.E.
        • Collins K.J.
        • Himmelfarb C.Dennison
        • DePalma S.M.
        • Gidding S.
        • Jamerson K.A.
        • Jones D.W.
        • MacLaughlin E.J.
        • Muntner P.
        • Ovbiagele B.
        • Smith S.C.
        • Spencer C.C.
        • Stafford R.S.
        • Taler S.J.
        • Thomas R.J.
        • Williams K.A.
        • Williamson J.D.
        • Wright J.T.
        2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines.
        Hypertens. Dallas Tex 1979. 2018; 71: 1269-1324https://doi.org/10.1161/HYP.0000000000000066
      1. (n.d.). https://www.heartfoundation.org.au/getmedia/c83511ab-835a-4fcf-96f5-88d770582ddc/PRO-167_Hypertension-guideline-2016_WEB.pdf
        • Giffin A.
        • Madden K.M.
        • Hogan D.B.
        Blood pressure targets for older patients-do advanced age and frailty really not matter?.
        Can. Geriatr. J. 2020; 23: 205-209https://doi.org/10.5770/cgj.23.429
        • Rabi D.M.
        • McBrien K.A.
        • Sapir-Pichhadze R.
        • Nakhla M.
        • Ahmed S.B.
        • Dumanski S.M.
        • Butalia S.
        • Leung A.A.
        • Harris K.C.
        • Cloutier L.
        • Zarnke K.B.
        • Ruzicka M.
        • Hiremath S.
        • Feldman R.D.
        • Tobe S.W.
        • Campbell T.S.
        • Bacon S.L.
        • Nerenberg K.A.
        • Dresser G.K.
        • Fournier A.
        • Burgess E.
        • Lindsay P.
        • Rabkin S.W.
        • Prebtani A.P.H.
        • Grover S.
        • Honos G.
        • Alfonsi J.E.
        • Arcand J.
        • Audibert F.
        • Benoit G.
        • Bittman J.
        • Bolli P.
        • Côté A.-M.
        • Dionne J.
        • Don-Wauchope A.
        • Edwards C.
        • Firoz T.
        • Gabor J.Y.
        • Gilbert R.E.
        • Grégoire J.C.
        • Gryn S.E.
        • Gupta M.
        • Hannah-Shmouni F.
        • Hegele R.A.
        • Herman R.J.
        • Hill M.D.
        • Howlett J.G.
        • Hundemer G.L.
        • Jones C.
        • Kaczorowski J.
        • Khan N.A.
        • Kuyper L.M.
        • Lamarre-Cliche M.
        • Lavoie K.L.
        • Leiter L.A.
        • Lewanczuk R.
        • Logan A.G.
        • Magee L.A.
        • Mangat B.K.
        • McFarlane P.A.
        • McLean D.
        • Michaud A.
        • Milot A.
        • Moe G.W.
        • Penner S.B.
        • Pipe A.
        • Poppe A.Y.
        • Rey E.
        • Roerecke M.
        • Schiffrin E.L.
        • Selby P.
        • Sharma M.
        • Shoamanesh A.
        • Sivapalan P.
        • Townsend R.R.
        • Tran K.
        • Trudeau L.
        • Tsuyuki R.T.
        • Vallée M.
        • Woo V.
        • Bell A.D.
        • Daskalopoulou S.S.
        Hypertension Canada's 2020 comprehensive guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children.
        Can. J. Cardiol. 2020; 36: 596-624https://doi.org/10.1016/j.cjca.2020.02.086
        • Delgado J.
        • Bowman K.
        • Ble A.
        • Masoli J.
        • Han Y.
        • Henley W.
        • Welsh S.
        • Kuchel G.A.
        • Ferrucci L.
        • Melzer D.
        Blood pressure trajectories in the 20 years before death.
        JAMA Intern. Med. 2018; 178: 93-99https://doi.org/10.1001/jamainternmed.2017.7023
        • Bari M.Di
        • van de Poll-Franse L.V.
        • Onder G.
        • Kritchevsky S.B.
        • Newman A.
        • Harris T.B.
        • Williamson J.D.
        • Marchionni N.
        • Pahor M.
        • <collab>Health Aging and Body Composition Studycollab
        Antihypertensive medications and differences in muscle mass in older persons: the Health, Aging and Body Composition Study.
        J. Am. Geriatr. Soc. 2004; 52: 961-966https://doi.org/10.1111/j.1532-5415.2004.52265.x
        • Caulfield L.
        • Heslop P.
        • Walesby K.E.
        • Sumukadas D.
        • Sayer A.A.
        • Witham M.D.
        Effect of angiotensin system inhibitors on physical performance in older people - a systematic review and meta-analysis.
        J. Am. Med. Dir. Assoc. 2020; https://doi.org/10.1016/j.jamda.2020.07.012
        • Cesari M.
        • Pedone C.
        • Incalzi R.A.
        • Pahor M.
        ACE-inhibition and physical function: results from the Trial of Angiotensin-Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study.
        J. Am. Med. Dir. Assoc. 2010; 11: 26-32https://doi.org/10.1016/j.jamda.2009.09.014
        • Chuang S.-Y.
        • Pan W.-H.
        • Chang H.-Y.
        • Wu C.-I.
        • Chen C.-Y.
        • Hsu C.-C.
        Protective effect of calcium channel blockers against frailty in older adults with hypertension.
        J. Am. Geriatr. Soc. 2016; 64: 1356-1358https://doi.org/10.1111/jgs.14155