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December 28, 1994, Vol 272, No. 24 >
ARTICLE | December 28, 1994

Hypertension in the Elderly: Title and subTitle BreakImplications and Generalizability of Randomized Trials FREE

Cynthia D. Mulrow, MD, MSc; John A. Cornell, PhD; Carlos R. Herrera, MD, MPH; Abdulmajead Kadri, PharmD; Lisa Farnett, PharmD; Christine Aguilar, MD, MPH
[+] Author Affiliations

Reprint requests to Audie L. Murphy Memorial Veterans Hospital, Ambulatory Care (11C6), 7400 Merton Minter Blvd, San Antonio, TX 78284 (Dr Mulrow),


JAMA. 1994;272(24):1932-1938. doi:10.1001/jama.1994.03520240060042
Text Size: A A A
Published online
Article
References

Objective.  —To estimate morbidity and mortality benefits of drug therapy for hypertensive elderly subjects, compare these benefits with effects in younger subjects, and provide a framework for generalizing results derived from trials to actual patients.

Data Sources.  —A literature search using MEDLINE from 1966 to 1993, references from reviews and trial articles, and experts.

Study Selection.  —Randomized trials lasting at least 1 year that evaluated effects of drug treatment on morbidity and mortality outcomes in hypertensive persons.

Data Extraction.  —Four independent reviewers appraised protocol characteristics and quality of selected trials.

Data Synthesis.  —There were 13 trials involving 16 564 elderly persons (age 60 years and older). The prevalence of cardiovascular risk factors, cardiovascular disease, and competing comorbid diseases was lower among trial participants than the general population of hypertensive elderly persons. When the six large high-quality trials were combined, trial results showed 43 subjects (95% confidence interval [CI], 31 to 69) and 61 subjects (95% CI, 39 to 141) needed to be treated for 5 years to prevent one cerebrovascular event and one coronary heart disease event, respectively. Including the other seven trials did not change the results significantly. Only 18 subjects (95% CI, 14 to 25) needed to be treated to prevent one cardiovascular event (cerebrovascular or cardiac). Twelve trials in primarily younger and middle-aged adults involved approximately 33 000 persons. For all outcomes except cardiac mortality, two to fourtimes as many of the younger subjects as the older subjects needed to be treated for 5 years to prevent morbid and mortal events. No significant effect on cardiac mortality was seen among younger subjects, while 78 older subjects (95% CI, 50 to 180) needed to be treated to prevent a fatal cardiac event.

Conclusions.  —Randomized trials demonstrate that treating healthy older persons with hypertension is highly efficacious. Five-year morbidity and mortality benefits derived from trials are greater for older than younger subjects. Extrapolating benefits from trials to individual patients is difficult, but should take into account multiple issues including the patient's risk factors, preexisting cardiovascular disease, and competing comorbid illnesses.(JAMA. 1994;272:1932-1938)

REFERENCES

1 +
Carter AB.  Hypotensive therapy in stroke survivors. Lancet . 1970;;1:485-489.
2 +
Veterans Administration Cooperative Study Group on Antihypertensive Agents.  Effects of treatment on morbidity in hypertension: influence of age, diastolic pressure, and prior cardiovascular disease: further analysis of side effects. Circulation . 1972;;45:991-1004.
3 +
Hypertension-Stroke Cooperative Study Group.  Effect of antihypertensive treatment on stroke recurrence. JAMA . 1974;;229:409-418.
4 +
Hypertension Detection and Follow-up Program Cooperative Group.  Five-year findings of the hypertension detection and follow-up program, II: mortality by race, sex, and age. JAMA . 1979;;242:2572-2577.
5 +
Sprackling ME, Mitchell JRA, Short AH, Watt G.  Blood pressure reduction in the elderly: a randomised controlled trial of methyldopa. BMJ . 1981;; 283:1151-1153.
6 +
Kuramoto K, Matsushita S, Kuwajima T, Murakami M.  Prospective study on the treatment of mild hypertension in the aged. Jpn Heart J . 1981;; 22:75-85.
7 +
Coope J, Warrender TS.  Randomised trial of treatment of hypertension in elderly patients in primary care. BMJ . 1986;;293:1145-1152.
8 +
The Management Committee.  Treatment of mild hypertension in the elderly: a study initiated and administered by the National Heart Foundation of Australia. Med J Aust . 1981;;2:398-402.
9 +
Amery A, Birkenhägen W, Brixko P, et al.  Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial. Lancet . 1985;;1:1349-1354.
10 +
Perry M, Schnaper HW, Schoenberger JA, Smith WM, Vogt TM, for the SHEP Research Group.  Systolic Hypertension in the Elderly Program (SHEP): antihypertensive efficacy of chlorthalidone. Am J Cardiol . 1985;;56:913-920.
11 +
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 . 1991;;265: 3255-3264.
12 +
Dahlof B, Lindholm LH, Hansson L, Schersten B, Ekbom T, Wester P-O.  Morbidity and mortality in the Swedish Trial in Old Patients With Hypertension (STOP-Hypertension). Lancet . 1991;;338: 1281-1285.
13 +
MRC Working Party.  Medical Research Council Trial of Treatment of Hypertension in Older Adults: principal results. BMJ . 1992;;304:405-412.
14 +
Materson BJ, Reda DJ, Cushman WC, et al.  Single-drug therapy for hypertension in men: a comparison of six antihypertensive agents with placebo. N Engl J Med . 1993;;328:914-921.
15 +
Yusuf S, Peto R, Lewis J, et al.  Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis . 1985;;27:335-371.
16 +
Laupacis A, Sackett DL, Roberts RS.  An assessment of clinically useful measures of the consequences of treatment. N Engl J Med . 1988;;318: 1728-1733.
17 +
Silberberg S, Henry DA.  The benefits of reducing cholesterol levels: the need to distinguish primary from secondary intervention, 2: implications for heart disease prevention in Australia. Med J Aust . 1991;;155:670-674.
18 +
DerSimonian R, Laird N.  Meta-analysis in clinical trials. Control Clin Trials . 1986;;7:177-188.
19 +
Collins R, Peto R, MacMahon S, et al.  Blood pressure, stroke, and coronary heart disease. Lancet . 1990;;335:827-838.
20 +
The Treatment of Mild Hypertension Research Group.  The Treatment of Mild Hypertension Study: a randomized, placebo-controlled trial of a nutritionalhygienic regimen along with various drug monotherapies. Arch Intern Med . 1991;;151:1413-1423.
21 +
Leren P, Helgeland A.  Oslo Hypertension Study. Drugs . 1986;;31( (suppl 1) ):41-45.
22 +
Australian National Blood Pressure Management Committee.  The Australian Therapeutic Trial in Mild Hypertension. Lancet . 1980;;1:1261-1267.
23 +
Medical Research Council Working Party.  MRC trial of treatment of mild hypertension: principal results. BMJ . 1985;;291:97-104.
24 +
Hypertension-Stroke Cooperative Study Group on Agents.  Effect of antihypertensive treatment on stroke recurrence. JAMA . 1974;;229:409-418.
25 +
Veterans Administration Cooperative Study Group on Antihypertensive Agents.  Effects of treatment on morbidity in hypertension, II: results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA . 1970;;213:1143-1152.
26 +
Barraclough M, Bainton D, Cochrane AL, et al.  Control of moderately raised blood pressure: report of a cooperative randomised controlled trial. BMJ . 1973;;3:434-436.
27 +
Veterans Administration Cooperative Study Group on Antihypertensive Agents.  Effects of treatment on morbidity in hypertension: results in patients with diastolic blood pressure averaging 115 through 129 mm Hg. JAMA . 1967;;202:1028-1034.
28 +
Wolff FW, Lindeman RD.  Effects of treatment in hypertension: results of a controlled study. J Chronic Dis . 1966;;19:227-240.
29 +
US Public Health Service Hospitals Cooperative Study Group.  Treatment of mild hypertension: results of a ten-year intervention trial. Circ Res . 1977;;40( (suppl 1) ):98-105.
30 +
Veterans Administration/National Heart, Lung, and Blood Institute Study Group for Evaluating Treatment in Mild Hypertension.  Evaluation of drug treatment in mild hypertension: VA-NHLBI feasibility trial. Ann N Y Acad Sci . 1978;;304:267-288.
31 +
Hypertension Detection and Follow-up Program Cooperative Group.  Five-year findings of the Hypertension Detection and Follow-up Program: reduction in mortality in persons with high blood pressure, including mild hypertension. JAMA . 1979;; 242:2562-2571.
32 +
Poulter N.  Management of multiple risk factors for coronary heart disease in patients with hypertension. Am Heart J . 1991;;121:246-250.
33 +
Kaplan NM, Weidmann P.  Is hypertension a metabolic disease? Am Heart J . 1993;;125:1485-1487.
34 +
Psaty BM, Savage PJ, Tell GS.  The Cardiovascular Health Study: temporal patterns of antihypertensive medication use among elderly patients. JAMA . 1993;;270:1837-1841.
35 +
Psaty BM, Furberg CD, Kuller LH.  Initial findings from the cardiovascular health study: isolated systolic hypertension and subclinical cardiovascular disease in the elderly. JAMA . 1992;;268:1287-1291.
36 +
Working Group on Management of Patients With Hypertension and High Blood Cholesterol.  National Education Programs Working Group report on the management of patients with hypertension and high blood cholesterol. Ann Intern Med . 1991;;114:224-237.
37 +
Levy D, Anderson K, Daniel DD, Kannel WB, Christiansen JC, Castelli WP.  Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. Ann Intern Med . 1988;;108: 7-13.
38 +
Mittelmark MB, Psaty BM, Rautaharju PM, et al.  The Cardiovascular Health Study: prevalence of cardiovascular diseases among older adults. Am J Epidemiol . 1993;;137:311-317.
39 +
Bild DE, Fitzpatrick A, Fried LP, et al.  Age-related trends in cardiovascular morbidity and physical functioning in the elderly: the Cardiovascular Health Study. J Am Geriatr Soc . 1993;;41:1047-1056.
40 +
Frohlich ED, Apstein, C, Chobanian, AV.  The heart in hypertension: medical progress. N Engl J Med . 1992;;327:998-1008.
41 +
 Comorbidity of chronic conditions and disability among older persons—United States, 1984. JAMA . 1990;;263:209-210.
42 +
MMWR Morbid Mortal Wkly Rep . 1989;;38:788-791.
43 +
US Dept of Health and Human Services. Healthy People 2000: National Health Promotion and Disease Prevention Objectives . Washington, DC: US Dept of Health and Human Services; 1990;:114-115. DHHS publication No. PHS 91-50212.
44 +
Stewart AL, Greenfield S, Hays RD, et al.  Functional status and well-being of patients with chronic conditions. JAMA . 1989;;262:907-913.
45 +
Denke MA, Sempos CT, Grundy SM.  Excess body weight: an underrecognized contributor to dyslipidemia in white American women. Arch Intern Med . 1994;;154:401-410.
46 +
Applegate WB.  The relative importance of focusing on elevations of systolic vs diastolic blood pressure. Arch Intern Med . 1992;;152:1969-1971.
47 +
Mann SJ.  Systolic hypertension in the elderly. Arch Intern Med . 1992;;152:1977-1984.
48 +
The Guidelines Subcommittee of the WHO/ISH Mild Hypertension Liaison Committee.  1993 guidelines for the management of mild hypertension: memorandum from a World Health Organization/ International Society of Hypertension meeting. Hypertension . 1993;;22:392-403.
49 +
Langford HG, Stamler J, Wassertheil-Smoller S, Prineas RJ.  All-cause mortality in the Hypertension Detection and Follow-up Program: findings in the whole cohort and for persons with less severe hypertension, with and without other traits related to risk of mortality. Prog Cardiovasc Dis . 1986;;29 ( (suppl 1) ):29-54.
50 +
Browner WS, Hulley SB.  Implications of hypertension trials: effect of risk status on treatment criteria. Hypertension . 1989;;13( (suppl 1) ):51-56.
51 +
Alderman MH.  Blood pressure management: Individualized treatment based on absolute risk and the potential for benefit. Ann Intern Med . 1993;; 119:329-335.
52 +
Alderman MH, Madhavan S.  Management of the hypertensive patient: a continuing dilemma. Hypertension . 1981;;3:192-197.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Carter AB.  Hypotensive therapy in stroke survivors. Lancet . 1970;;1:485-489.
2 +
Veterans Administration Cooperative Study Group on Antihypertensive Agents.  Effects of treatment on morbidity in hypertension: influence of age, diastolic pressure, and prior cardiovascular disease: further analysis of side effects. Circulation . 1972;;45:991-1004.
3 +
Hypertension-Stroke Cooperative Study Group.  Effect of antihypertensive treatment on stroke recurrence. JAMA . 1974;;229:409-418.
4 +
Hypertension Detection and Follow-up Program Cooperative Group.  Five-year findings of the hypertension detection and follow-up program, II: mortality by race, sex, and age. JAMA . 1979;;242:2572-2577.
5 +
Sprackling ME, Mitchell JRA, Short AH, Watt G.  Blood pressure reduction in the elderly: a randomised controlled trial of methyldopa. BMJ . 1981;; 283:1151-1153.
6 +
Kuramoto K, Matsushita S, Kuwajima T, Murakami M.  Prospective study on the treatment of mild hypertension in the aged. Jpn Heart J . 1981;; 22:75-85.
7 +
Coope J, Warrender TS.  Randomised trial of treatment of hypertension in elderly patients in primary care. BMJ . 1986;;293:1145-1152.
8 +
The Management Committee.  Treatment of mild hypertension in the elderly: a study initiated and administered by the National Heart Foundation of Australia. Med J Aust . 1981;;2:398-402.
9 +
Amery A, Birkenhägen W, Brixko P, et al.  Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial. Lancet . 1985;;1:1349-1354.
10 +
Perry M, Schnaper HW, Schoenberger JA, Smith WM, Vogt TM, for the SHEP Research Group.  Systolic Hypertension in the Elderly Program (SHEP): antihypertensive efficacy of chlorthalidone. Am J Cardiol . 1985;;56:913-920.
11 +
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 . 1991;;265: 3255-3264.
12 +
Dahlof B, Lindholm LH, Hansson L, Schersten B, Ekbom T, Wester P-O.  Morbidity and mortality in the Swedish Trial in Old Patients With Hypertension (STOP-Hypertension). Lancet . 1991;;338: 1281-1285.
13 +
MRC Working Party.  Medical Research Council Trial of Treatment of Hypertension in Older Adults: principal results. BMJ . 1992;;304:405-412.
14 +
Materson BJ, Reda DJ, Cushman WC, et al.  Single-drug therapy for hypertension in men: a comparison of six antihypertensive agents with placebo. N Engl J Med . 1993;;328:914-921.
15 +
Yusuf S, Peto R, Lewis J, et al.  Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis . 1985;;27:335-371.
16 +
Laupacis A, Sackett DL, Roberts RS.  An assessment of clinically useful measures of the consequences of treatment. N Engl J Med . 1988;;318: 1728-1733.
17 +
Silberberg S, Henry DA.  The benefits of reducing cholesterol levels: the need to distinguish primary from secondary intervention, 2: implications for heart disease prevention in Australia. Med J Aust . 1991;;155:670-674.
18 +
DerSimonian R, Laird N.  Meta-analysis in clinical trials. Control Clin Trials . 1986;;7:177-188.
19 +
Collins R, Peto R, MacMahon S, et al.  Blood pressure, stroke, and coronary heart disease. Lancet . 1990;;335:827-838.
20 +
The Treatment of Mild Hypertension Research Group.  The Treatment of Mild Hypertension Study: a randomized, placebo-controlled trial of a nutritionalhygienic regimen along with various drug monotherapies. Arch Intern Med . 1991;;151:1413-1423.
21 +
Leren P, Helgeland A.  Oslo Hypertension Study. Drugs . 1986;;31( (suppl 1) ):41-45.
22 +
Australian National Blood Pressure Management Committee.  The Australian Therapeutic Trial in Mild Hypertension. Lancet . 1980;;1:1261-1267.
23 +
Medical Research Council Working Party.  MRC trial of treatment of mild hypertension: principal results. BMJ . 1985;;291:97-104.
24 +
Hypertension-Stroke Cooperative Study Group on Agents.  Effect of antihypertensive treatment on stroke recurrence. JAMA . 1974;;229:409-418.
25 +
Veterans Administration Cooperative Study Group on Antihypertensive Agents.  Effects of treatment on morbidity in hypertension, II: results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA . 1970;;213:1143-1152.
26 +
Barraclough M, Bainton D, Cochrane AL, et al.  Control of moderately raised blood pressure: report of a cooperative randomised controlled trial. BMJ . 1973;;3:434-436.
27 +
Veterans Administration Cooperative Study Group on Antihypertensive Agents.  Effects of treatment on morbidity in hypertension: results in patients with diastolic blood pressure averaging 115 through 129 mm Hg. JAMA . 1967;;202:1028-1034.
28 +
Wolff FW, Lindeman RD.  Effects of treatment in hypertension: results of a controlled study. J Chronic Dis . 1966;;19:227-240.
29 +
US Public Health Service Hospitals Cooperative Study Group.  Treatment of mild hypertension: results of a ten-year intervention trial. Circ Res . 1977;;40( (suppl 1) ):98-105.
30 +
Veterans Administration/National Heart, Lung, and Blood Institute Study Group for Evaluating Treatment in Mild Hypertension.  Evaluation of drug treatment in mild hypertension: VA-NHLBI feasibility trial. Ann N Y Acad Sci . 1978;;304:267-288.
31 +
Hypertension Detection and Follow-up Program Cooperative Group.  Five-year findings of the Hypertension Detection and Follow-up Program: reduction in mortality in persons with high blood pressure, including mild hypertension. JAMA . 1979;; 242:2562-2571.
32 +
Poulter N.  Management of multiple risk factors for coronary heart disease in patients with hypertension. Am Heart J . 1991;;121:246-250.
33 +
Kaplan NM, Weidmann P.  Is hypertension a metabolic disease? Am Heart J . 1993;;125:1485-1487.
34 +
Psaty BM, Savage PJ, Tell GS.  The Cardiovascular Health Study: temporal patterns of antihypertensive medication use among elderly patients. JAMA . 1993;;270:1837-1841.
35 +
Psaty BM, Furberg CD, Kuller LH.  Initial findings from the cardiovascular health study: isolated systolic hypertension and subclinical cardiovascular disease in the elderly. JAMA . 1992;;268:1287-1291.
36 +
Working Group on Management of Patients With Hypertension and High Blood Cholesterol.  National Education Programs Working Group report on the management of patients with hypertension and high blood cholesterol. Ann Intern Med . 1991;;114:224-237.
37 +
Levy D, Anderson K, Daniel DD, Kannel WB, Christiansen JC, Castelli WP.  Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. Ann Intern Med . 1988;;108: 7-13.
38 +
Mittelmark MB, Psaty BM, Rautaharju PM, et al.  The Cardiovascular Health Study: prevalence of cardiovascular diseases among older adults. Am J Epidemiol . 1993;;137:311-317.
39 +
Bild DE, Fitzpatrick A, Fried LP, et al.  Age-related trends in cardiovascular morbidity and physical functioning in the elderly: the Cardiovascular Health Study. J Am Geriatr Soc . 1993;;41:1047-1056.
40 +
Frohlich ED, Apstein, C, Chobanian, AV.  The heart in hypertension: medical progress. N Engl J Med . 1992;;327:998-1008.
41 +
 Comorbidity of chronic conditions and disability among older persons—United States, 1984. JAMA . 1990;;263:209-210.
42 +
MMWR Morbid Mortal Wkly Rep . 1989;;38:788-791.
43 +
US Dept of Health and Human Services. Healthy People 2000: National Health Promotion and Disease Prevention Objectives . Washington, DC: US Dept of Health and Human Services; 1990;:114-115. DHHS publication No. PHS 91-50212.
44 +
Stewart AL, Greenfield S, Hays RD, et al.  Functional status and well-being of patients with chronic conditions. JAMA . 1989;;262:907-913.
45 +
Denke MA, Sempos CT, Grundy SM.  Excess body weight: an underrecognized contributor to dyslipidemia in white American women. Arch Intern Med . 1994;;154:401-410.
46 +
Applegate WB.  The relative importance of focusing on elevations of systolic vs diastolic blood pressure. Arch Intern Med . 1992;;152:1969-1971.
47 +
Mann SJ.  Systolic hypertension in the elderly. Arch Intern Med . 1992;;152:1977-1984.
48 +
The Guidelines Subcommittee of the WHO/ISH Mild Hypertension Liaison Committee.  1993 guidelines for the management of mild hypertension: memorandum from a World Health Organization/ International Society of Hypertension meeting. Hypertension . 1993;;22:392-403.
49 +
Langford HG, Stamler J, Wassertheil-Smoller S, Prineas RJ.  All-cause mortality in the Hypertension Detection and Follow-up Program: findings in the whole cohort and for persons with less severe hypertension, with and without other traits related to risk of mortality. Prog Cardiovasc Dis . 1986;;29 ( (suppl 1) ):29-54.
50 +
Browner WS, Hulley SB.  Implications of hypertension trials: effect of risk status on treatment criteria. Hypertension . 1989;;13( (suppl 1) ):51-56.
51 +
Alderman MH.  Blood pressure management: Individualized treatment based on absolute risk and the potential for benefit. Ann Intern Med . 1993;; 119:329-335.
52 +
Alderman MH, Madhavan S.  Management of the hypertensive patient: a continuing dilemma. Hypertension . 1981;;3:192-197.

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