Hypertension in the Elderly

Clinics in Geriatric Medicine

Volumn 25, Issue 3, 2009, Pages 391-412

  Acelajado, Maria Czarina ^a   Oparil, Suzanne ^a  

^a Vascular Biology and Hypertension Program   (United States)

Author keywords

Diagnosis; Elderly; Hypertension; Management; Pathophysiology

Indexed keywords

ACETYLSALICYLIC ACID; ALDOSTERONE ANTAGONIST; AMLODIPINE; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIDEPRESSANT AGENT; ATENOLOL; BENAZEPRIL; BENDROFLUMETHIAZIDE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; CARVEDILOL; CHLORTALIDONE; CYCLOOXYGENASE 2 INHIBITOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; DOXAZOSIN; ENALAPRIL; HYDROCHLOROTHIAZIDE; INDAPAMIDE; INDOMETACIN; LISINOPRIL; LOSARTAN; NEBIVOLOL; NITRENDIPINE; NONSTEROID ANTIINFLAMMATORY AGENT; PERINDOPRIL; PIROXICAM; PLACEBO; THIAZIDE DIURETIC AGENT; UNINDEXED DRUG;

ADRENERGIC SYSTEM; AEROBIC EXERCISE; AGED; ARTERIAL STIFFNESS; BLOOD PRESSURE; BLOOD PRESSURE REGULATION; CARDIOVASCULAR DISEASE; CEREBROVASCULAR ACCIDENT; CHRONIC KIDNEY DISEASE; CLINICAL TRIAL; COGNITIVE DEFECT; CORONARY ARTERY DISEASE; DEMENTIA; DIABETES MELLITUS; DISEASE CLASSIFICATION; DRUG ANTAGONISM; DRUG EFFICACY; DYSLIPIDEMIA; GLUCOSE BLOOD LEVEL; HEART FAILURE; HUMAN; HYPERTENSION; HYPOKALEMIA; HYPONATREMIA; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LOW DRUG DOSE; ORTHOSTATIC HYPOTENSION; OSTEOARTHRITIS; PATIENT COMPLIANCE; PLASMA RENIN ACTIVITY; PULSE PRESSURE; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK REDUCTION; SIDE EFFECT; SODIUM LOAD; SODIUM RESTRICTION; SYSTOLIC BLOOD PRESSURE;

AGE FACTORS; AGED; ANTIHYPERTENSIVE AGENTS; BLOOD PRESSURE; EXERCISE THERAPY; HUMANS; HYPERTENSION; INCIDENCE; LIFE STYLE; PREVALENCE; PROGNOSIS; RISK FACTORS; SURVIVAL RATE;

EID: 70249139157     PISSN: 07490690     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cger.2009.06.001     Document Type: Review

References (111)

1. Lewington S., Clarke R., Qizilbash N., et al., for the Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for 1 million adults in 61 prospective studies. Lancet 360 (2002) 1903-1913
2. Whelton P.K., He J., Appel L.J., et al. Primary prevention of hypertension: clinical and public health advisory from the National High Blood Pressure Education Program. JAMA 288 (2002) 1882-1888
3. Ostchega Y., Dillon C.F., Hughes J.P., et al. Trends in hypertension prevalence, awareness, treatment, and control in older U.S. adults: data from the National Health and Nutrition Examination Survey 1988 to 2004. J Am Geriatr Soc 55 (2007) 1056-1065
4. Vasan R.S., Beiser A., Seshadri S., et al. Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham Heart Study. JAMA 287 (2002) 1003-1010
5. National High Blood Pressure Education Program Working Group. National High Blood Pressure Education Program Working Group report on hypertension in the elderly. Hypertension 23 3 (1994) 275-285
6. Staessen J.A., Gasowski J., Wang J.G., et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet 355 (2000) 865-872
7. Pastor-Barriuso R., Banegas J.R., Damian J., et al. Systolic blood pressure, diastolic blood pressure, and pulse pressure: an evaluation of their joint effect on mortality. Ann Intern Med 139 (2003) 731-739
8. Psaty B.M., Furberg C.D., Kuller L.H., et al. Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality. Arch Intern Med 161 (2001) 1183-1192
9. Domanski M.J., Davis B.R., Pfeffer M.A., et al. Isolated systolic hypertension: prognostic information provided by pulse pressure. Hypertension 34 (1999) 375-380
10. Franklin S.S., Larson M.G., Khan S.A., et al. Does the relationship of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study. Circulation 103 9 (2001) 1245-1249
11. Franklin S.S., Lopez V.A., Wong N.D., et al. Single versus combined blood pressure components and risk for CVD. The Framingham Heart Study. Circulation 119 (2009) 243-250
12. Dao H.H., Essalihi R., Bouvet C., et al. Evolution and modulation of age-related medial elastocalcinosis: impact on large artery stiffness and isolated systolic hypertension. Cardiovasc Res 66 (2005) 307-317
13. Mitchell G.F., Parise H., Benjamin E.J., et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study. Hypertension 43 (2004) 1239-1245
14. Nichols W.W., and O'Rourke M.F. Wave reflections. McDonald's blood flow in the arteries (2005), Hodder Headline Group, London p. 193
15. Schriffin E.L. Vascular stiffening and arterial compliance. Am J Hypertens 17 (2004) 39S-48S
16. Wang X., Keith J.C., Struthers A.D., et al. Assessment of arterial stiffness, a translational medicine biomarker system for evaluation of vascular risk. Cardiovasc Ther 26 (2008) 214-223
17. Laurent S., Boutouyrie P., Asmar R., et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 37 (2001) 1236-1241
18. Sutton-Tyrrell K., Najjar S.S., Boudreau R.M., et al. Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults. Circulation 111 (2005) 3384-3390
19. Taddei S., Virdis A., Mattei P., et al. Aging and endothelial function in normotensive subjects and essential hypertensive subjects. Circulation 91 (1995) 1981-1987
20. Walsh M.B., Donnelly T., and Lyons D. Impaired endothelial nitric oxide bioavailability: a common link between aging, hypertension and atherogenesis?. J Am Geriatr Soc 57 (2009) 140-145
21. Wallace S.M.L., Yasmin, McEniery C.M., et al. Isolated systolic hypertension is characterized by increased aortic stiffness and endothelial dysfunction. Hypertension 50 (2007) 228-233
22. Epstein M., and Hollenberg N.K. Age as a determinant of renal sodium conservation in normal man. J Lab Clin Med 87 (1976) 411-417
23. Zemel M.B., and Sowers J.R. Salt sensitivity and systemic hypertension in the elderly. Am J Cardiol 61 16 (1988) 7H-12H
24. Anderson D.E., Fedorova O.V., Morrell C.H., et al. Endogenous sodium pump inhibitors and age-associated increases in salt sensitivity of blood pressure in normotensives. Am J Physiol Regul Integr Comp Physiol 294 (2008) R1248-R1254
25. Luft F.C., Miller J.Z., Weinberger M.H., et al. Genetic influences on the response to dietary sodium reduction, acute salt loading, or salt depletion in humans. J Cardiovasc Pharmacol 12 3 (1988) S49-S55
26. Dengel D.R., Brown M.D., Ferrell R.E., et al. Role of angiotensin converting enzyme genotype in sodium sensitivity in older hypertensives. Am J Hypertens 14 (2001) 1178-1184
27. Colylewright M., Reckelhoff J.E., and Ouyang P. Menopause and hypertension an age-old debate. Hypertension 51 (2008) 952-959
28. Weidmann P., De Mytternere-Burstein S., Maxwell M.H., et al. Effect of aging on plasma renin and aldosterone in normal men. Kidney Int 8 (1975) 325-333
29. Wilson T.W., McCaulay F.A., and Waslen T.A. Effects of aging on responses to furosemide. Prostaglandins 38 (1989) 675-687
30. Epstein M. Aging and the kidney. J Am Soc Nephrol 43 7 (1992) 1100-1122
31. Seals D.R., and Esler M.D. Human ageing and the sympathoadrenal system. J Physiol 528 3 (2000) 407-417
32. Chobanian A.V., Bakris G.L., Black H.R., et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 42 (2003) 1206-1252
33. Klag M.J., Whelton P.K., Randall B.L., et al. Blood pressure and end-stage renal disease in men. N Engl J Med 334 (1996) 13-18
34. Young J.H., Klag M.J., Muntner P., et al. Blood pressure and decline in kidney function: findings from the Systolic Hypertension in the Elderly Program (SHEP). J Am Soc Nephrol 13 (2002) 2776-2782
35. De Leeuw P.W., Lutgarde T., Birkenhager W.H., et al. Prognostic significance of renal function in elderly patients with isolated systolic hypertension: results from the Syst-Eur trial. J Am Soc Nephrol 13 (2002) 2213-2222
36. Verhave J.C., Fesler P., du Cailar G., et al. Elevated pulse pressure is associated with low renal function in elderly patients with isolated systolic hypertension. Hypertension 45 (2005) 586-591
37. Cheng L., Gao Y., Gu Y., et al. Stepwise increase in the prevalence of isolated systolic hypertension with the stages of chronic kidney disease. Nephrol Dial Transplant 23 (2008) 3895-3900
38. Turnbull F., et al., Blood Pressure Lowering Trialists' Collaboration. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomized trials. BMJ 336 (2008) 1121-1123
39. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 265 (1991) 3255-3264
40. Staessen J.A., Fagard R., Thijs L., et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 350 (1997) 757-764
41. Liu L., Wang J.G., Gong L., et al. Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. J Hypertens 16 (1998) 1823-1829
42. Lithell H., Hansson L., Skoog I., et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 21 (2003) 875-886
43. Ungar A., Pepe G., Lambertucci L., et al. Low diastolic ambulatory blood pressure is associated with greater all-cause mortality in older patients with hypertension. J Am Geriatr Soc 57 (2009) 291-296
44. Cushman W.C., Cutler J.A., Hanna E., et al. Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure. Arch Intern Med 58 (1998) 1197-1207
45. Whelton P.K., Appel L.J., Espeland M.A., et al. Sodium reduction and weight loss in the treatment of hypertension in older persons. JAMA 279 (1998) 839-846
46. Cappuccio F.P., Markandu N.D., Carney C., et al. Double blind randomised trial of modest salt restriction in older people. Lancet 350 (1997) 850-854
47. Westhoff T.H., Franke N., Schmidt S., et al. Too old to benefit from sports? The cardiovascular effects of exercise training in elderly subjects treated for isolated systolic hypertension. Kidney Blood Press Res 30 (2007) 240-247
48. Cook N.R., Cutler J.A., Obarzanek E., et al. Long-term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the Trials Of Hypertension Prevention (TOHP). BMJ 334 (2007) 885
49. Cook N.R., Obarzenek E., Cutler J.A., et al. Joint effects of sodium and potassium intake on subsequent cardiovascular disease. Arch Intern Med 169 1 (2009) 32-40
50. Grobbee D.E., and Hofman A. Does sodium restriction lower blood pressure?. Br Med J 293 (1986) 27-30
51. Gates P.E., Tanaka H., Hiatt W.R., et al. Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension. Hypertension 44 (2004) 35-41
52. Appel L.J., Moore T.J., Obarzanek E., et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 336 (1997) 1117-1124
53. Appel LJ on behalf of the American Society of Hypertension Writing Group. ASH Position Paper on dietary approaches to prevent and treat hypertension. J Clin Hypertens, Accessed June 18, 2009. DOI 10.1111/j.1751-7176.2009.00136.X.
54. Applegate W.B., Miller S.T., Elam J.T., et al. Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension. Arch Intern Med 152 (1992) 1162-1166
55. Patel A.B., Kostis J.B., Wilson A.C., et al. Fourteen-year follow-up of the Systolic Hypertension in the Elderly Program. Stroke 39 (2008) 1084-1089
56. Staessen J.A., Thijs L., Fagard R., et al. Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial. J Hypertens 22 (2004) 847-857
57. Furberg C.D., Wright J.T., Davis B.R., et al., for the ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker versus diuretic. JAMA 288 (2002) 2981-2997
58. Costanzo L.S. Localization of diuretic action in microperfused rat distal tubules: Ca and Na transport. Am J Physiol 248 (1985) F527-F535
59. Ray W.A., Griffin M.R., Downey W., et al. Long-term use of thiazide diuretics and risk of hip fracture. Lancet 1 (1989) 687-690
60. Wanich R., Davis J., Ross P., et al. Effects of thiazides on rates of bone mineral loss: a longitudinal study. Br Med J 310 (1990) 1303-1305
61. Reid I.R., Ames I.W., Orr-Walker B.J., et al. Hydrochlorothiazide reduces loss of cortical bone in normal post-menopausal women: a randomized controlled trial. Am J Med 109 (2000) 362-370
62. Poon I.O., and Braun U. High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans. J Clin Pharm Ther 30 (2005) 173-178
63. Lind L., Pollare T., Berne C., et al. Long-term metabolic effects of hypertensive drugs. Am Heart J 128 (1994) 1177-1183
64. Black H.R., Davis B., Barzilay J., et al. Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine or lisinopril as initial treatment for hypertension. Diabetes Care 31 (2008) 353-360
65. Barzilay J.I., Davis B.R., Cutler J.A., et al. Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment. Arch Intern Med 166 (2006) 2191-2201
66. Kostis J.B., Wilson A.C., Freudenberger R.S., et al. Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes. Am J Cardiol 95 (2005) 29-35
67. Gianni M., Bosch J., Pogue J., et al. Effects of long-term ACE inhibitor therapy in elderly vascular disease patients. Eur Heart J 28 (2007) 1382-1388
68. Dahlof B., Devereux R.B., Kjeldsen S.E., et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 359 (2002) 995-1003
69. Bang L.E., Winberg N., Wachtell K., et al. Losartan versus atenolol on 24-hour ambulatory blood pressure. A LIFE substudy. Blood Press 16 (2007) 392-397
70. Dahlof B., Sever P.S., Poulter N.R., et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding benzoflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomized controlled trial. Lancet 366 (2005) 895-906
71. Jamerson K., Weber M.A., Bakris G.L., et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 359 23 (2008) 2417-2428
72. Jamerson K.A., and Weber M.A. Benazepril plus amlodipine or hydrochlorothiazide for hypertension. N Engl J Med 360 (2009) 1147-1150 Correspondence
73. Lindholm L.H., Carlberg B., and Samuelsson O. Should β-blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 366 (2005) 1545-1553
74. Messerli F.H., Grossman E., and Goldbourt U. Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review. JAMA 279 23 (1998) 1903-1907
75. Dhakam Z., Yasmin, McEniery C.M., et al. A comparison of atenolol and nebivolol in isolated systolic hypertension. J Hypertens 26 2 (2008) 351-356
76. Jawa A., Nachimuthu S., Pendergrass M., et al. Beta blockers have a beneficial effect upon endothelial function and microalbuminuria in African American subjects with diabetes and hypertension. J Diabet Complications 22 5 (2008) 303-308
77. Bakris G.L., Fonseca V., Katholi R.E., et al. Metabolic effects of carvedilol versus metoprolol in patients with type 2 diabetes and hypertension. JAMA 292 (2004) 2227-2236
78. Oparil S., and Weber M. Angiotensin receptor blocker and dihydropyridine calcium channel blocker combinations: an emerging strategy in hypertension therapy. Postgrad Med 121 (2009) 25-39
79. Dickson M., and Plauschinat C.A. Compliance with antihypertensive therapy in the elderly. Am J Cardiovasc Drugs 8 1 (2008) 45-50
80. Ernst M.E., Carter B.L., Goerdt C.J., et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension 47 (2006) 352-358
81. Bartsch G.E., Broste S.K., Grandits G.A., et al. Hydrochlorothiazide, chlorthalidone and mortality in the Multiple Risk Factor Intervention Trial. Circulation 70 Suppl II (1984) II-360
82. Multiple Risk Factor Intervention Trial Research Group. Mortality after 101/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial. Circulation 82 (1990) 1616-1628
83. Angela F., Verdecchia P., Riboldi G.P., et al. Calcium channel blockade to prevent stroke in hypertension. Am J Hypertens 17 (2004) 817-822
84. Wald L.J., and Law M.R. A strategy to reduce cardiovascular disease by more than 80%. BMJ 326 (2003) 1419
85. Yusuf S., Pais P., Afzal R., et al. Effects of a polypill (Polycap) on risk factors in middle aged individuals without cardiovascular disease (TIPS): a phase II, double blind, randomized trial. Lancet 373 (2009) 1341-1351
86. Dahlof B., Hansson L., Lindholm L.H., et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 338 (1991) 1281-1285
87. Gueyffier F., Bulpitt C., Boissel J., et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. Lancet 353 (1999) 793-796
88. Beckett N.S., Peters R., Flaetcher A.E., et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 358 18 (2008) 1887-1898
89. DiMatteo M.R. Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care 42 (2004) 200-209
90. Kripalani S., Yao X., and Haynes R.B. Interventions to enhance medication adherence in chronic medical conditions. A systematic review. Arch Intern Med 167 (2007) 540-550
91. Chapman R.H., Petrilla A.A., Benner J.S., et al. Predictors of adherence to concomitant antihypertensive and lipid-lowering medications in older adults: a retrospective, cohort study. Drugs Aging 25 10 (2008) 885-892
92. Bangalore S., Kamalakkannan G., Parkar S., et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 120 8 (2007) 713-719
93. Banning M. Older people and adherence to medication: a review of the literature. Int J Nurs Stud 45 (2008) 1550-1561
94. Frishman W.H. Effects of nonsteroidal antiinflammatory drug therapy on blood pressure and peripheral edema. Am J Cardiol 89 (2002) 18D-25D
95. Ishiguro C., Fukita T., Omori T., et al. Assessing the effects of nonsteroidal antiinflammatory drugs on antihypertensive drug therapy using post-marketing surveillance database. J Epidemiol 18 3 (2008) 119-124
96. Pavlicevic I., Kuzmanic M., Rumboldt M., et al. Interaction between antihypertensives and NSAIDS in primary care: a controlled trial. Can J Clin Pharmacol 15 3 (2008) e372-e382
97. Wilson S.L., and Poulter N.R. The effect of nonsteroidal antiinflammatory drugs and other commonly used nonnarcotic analgesics on blood pressure levels in adults. J Hypertens 24 (2006) 1457-1469
98. Whelton A., White W.B., Bello A.E., et al. Effects of celecoxib and rofecoxib on blood pressure and edema in patients 65 years of age with systemic hypertension and osteoarthritis. Am J Cardiol 90 (2002) 959-963
99. Morgan T.O., Anderson A., and Bertram D. Effects of indomethacin on blood pressure in elderly people with essential hypertension well-controlled with amlodipine or enalapril. Am J Hypertens 13 (2000) 1161-1167
100. Avancini F., Palumbo G., Alli C., et al. Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Am J Hypertens 13 (2000) 611-616
101. Beckett N.S., Connor M., Sadler J.D., et al. Orthostatic fall in blood pressure in the very elderly hypertensive: results from the Hypertension in the Very Elderly Trial (HYVET)-pilot. J Hum Hypertens 13 (1999) 839-840
102. Hiitola P., Enlund H., Kettunen R., et al. Postural changes in blood pressure and the prevalence of orthostatic hypotension among home-dwelling elderly aged 75 years or older. J Hum Hypertens 23 (2009) 33-39
103. Cohen I., Rogers P., Burke B., et al. Predictors of medication use, compliance and symptoms of hypotension in a community-based sample of elderly men and women. J Clin Pharm Ther 23 (1998) 423-432
104. Rutan G.H., Hermanson B., Bild D.E., et al. Orthostatic hypotension in older adults. The Cardiovascular Health Study. Hypertension 19 (1992) 508-519
105. Kaplan D.T., Furman M.I., Pincus S.M., et al. Aging and the complexity of cardiovascular dynamics. Biophys J 59 (1991) 945-949
106. Shi X., Wray W., Formes K.J., et al. Orthostatic hypotension in aging humans. Am J Physiol Heart Circ Physiol 279 (2000) H1548-H1554
107. Fratiglioni L., De Ronchi D., and Agüero-Torres H. World-wide prevalence and incidence of dementia. Drugs Aging 15 (1999) 365-375
108. Launer L., Masaki K., Petrovitch H., et al. The association between midlife blood pressure levels and late-life cognitive function. JAMA 274 (1995) 1846-1851
109. Qiu C., Winblad B., and Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 4 (2005) 487-499
110. Forette F., Seux M., Staessen J., et al. Prevention of dementia in a randomised double blind placebo controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 352 (1998) 1347-1351
111. Peters R., Beckett N., Forette F., et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol 7 (2008) 683-689