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ARTICLE |

Antihypertensive Therapy: Title and subTitle BreakTo Stop or Not to Stop? FREE

Roland E. Schmieder, MD; Jurgen K. Rockstroh, MD; Franz H. Messerli, MD
[+] Author Affiliations

Reprint requests to Department of Medicine, University of Erlangen-Nürnberg, Kontumazgarten 14-18, D8500 Nürnberg 80, Federal Republic of Germany (Dr Schmieder).


JAMA. 1991;265(12):1566-1571. doi:10.1001/jama.1991.03460120080040
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Published online

The benefits of continuous antihypertensive therapy have been extensively documented. However, lack of compliance with the prescribed regimen, excessive cost, and troublesome adverse effects of some antihypertensive agents led to the consideration of intermittent therapy or even complete discontinuation of therapy as an effective alternative to lifelong medication. Prospective studies dealing with this subject reported inconsistent results. Nevertheless, they allowed us to identify selection criteria of candidates for step-down or discontinuation of antihypertensive therapy. Such candidates include patients with mild essential hypertension who have one or more of the following characteristics: young age, normal body weight, low salt intake, no alcohol consumption, low pretreatment blood pressure, successful therapy with one drug only, and no or only minimal signs of target organ damage. Stopping antihypertensive therapy without subsequent rise in arterial pressure was shown to be possible in a subset of patients with mild essential hypertension for a period of months to years. This approach appears to be safe, provided that blood pressure is monitored frequently, and may improve compliance, save treatment costs, and reduce adverse effects of certain drugs, although its long-term consequences for morbidity and mortality remain to be determined.

(JAMA. 1991;265:1566-1571)

REFERENCES

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.
Helgeland A.  Treatment of mild hypertension: a 5 year controlled drug trial: the Oslo study . Am J Med. 1980;;69:725-732.
Hypertension Detection and Follow-up Program Cooperative Group.  Five year findings of the Hypertension Detection and Follow-up Program, I: reduction in mortality of persons with high blood pressure, including mild hypertension . JAMA. 1979;;242:2562-2571.
European Working Party on High Blood Pressure in the Elderly.  Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial . Lancet. 1985;;1:1349-1354.
 Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results . BMJ. 1985;;291:97-104.
MacMahon SW, Cutter JA, Neaton JD, Payne GH.  Relationship of blood pressure to coronary and stroke morbidity and mortality in clinical trials and epidemiological studies . J Hypertens. 1986;;4( (suppl 6) ):14-17.
Cruickshank JM.  Why has the primary prevention of myocardial infarction in the treatment of hypertension been so elusive ? J Hum Hypertens. 1987;;1:73-81.
Beckenridge A.  Compliance of hypertensive patients with pharmacological treatment . Hypertension. 1983;;5( (suppl III) ):85-89.
Multiple Risk Factor Intervention Trial Research Group.  Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial . Am J Cardiol. 1985;;55:1-15.
Hollifield JW.  Potassium and magnesium abnormalities: diuretics and arrhythmias in hypertension . Am J Med. 1984;;77( (suppl 5A) ):28-32.
Grimm RH Jr, Leon AS, Hunninghake DB, Lenz K, Hannan P, Blackburn H.  Effects of thiazide diuretics on plasma lipids and lipoproteins in mildly hypertensive patients: a double-blind controlled trial . Ann Intern Med. 1981;;94:7-11.
Finnerty FA Jr.  Step-down treatment of mild systemic hypertension . Am J Cardiol. 1984;;53: 1304-1307.
 Veterans Administration Cooperative Study Group on Antihypertensive Agents. Return of elevated blood pressure after withdrawal of antihypertensive drugs . Circulation. 1975;;51:1107-1113.
Stamler R, Stamler J, Grimm R, et al.  Trial on control of hypertension by nutritional means: three-year results . J Hypertens. 1984;;2( (suppl 3) ):167-170.
 Medical Research Council Working Party on Mild Hypertension. Course of blood pressure in mild hypertensives after withdrawal of long term antihypertensive treatment . BMJ. 1986;;293:988-992.
Stamler R, Stamler J, Grimm R, et al.  Nutritional therapy for high blood pressure: final report of a 4-year randomized controlled trial—The Hypertension Control Program . JAMA. 1987;;257: 1484-1491.
Freis ED, Thomas JR, Fisher SG, et al.  Effects of reduction in drugs or dosage after long-term control of systemic hypertension . Am J Cardiol. 1989;;63:702-708.
Zanchetti A.  Treatment goals in hypertension . Am J Med. 1984;;76:1-3.
The Joint National Committee on Detection,  Evaluation, and Treatment of High Blood Pressure. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure . Arch Intern Med. 1988;;148: 1023-1038.
Page IH, Dustan HP.  Persistence of normal blood pressure after discontinuing treatment in hypertensive patients . Circulation. 1962;;25:433-436.
Perry HM Jr, Schroeder HA, Catanzaro FJ, Moore-Jones D.  Studies on the control of hypertension, VIII: mortality, morbidity, and remissions during 12 years of intensive therapy . Circulation. 1966;;33:958-972.
Thurm RH, Smith WM.  On resetting of'barostats' in hypertensive patients . JAMA. 1967;;201: 301-304.
Dustan HP, Page IH, Tarazi RC, Frohlich ED.  Arterial pressure responses to discontinuing antihypertensive drugs . Circulation. 1968;;37:370-379.
Boyle RM, Price ML, Hamilton M.  Thiazide withdrawal in hypertension . J R Coll Physicians Lond. 1979;;13:172-173.
Levinson PD, Khatri IM, Freis ED.  Persistence of normal BP after withdrawal of drug treatment in mild hypertension . Arch Intern Med. 1982;;142:2265-2268.
Fernandez PG, Kim BK, Galway AB, Sharma JN.  Separation of essential hypertensive patients based on blood pressure responses after the withdrawal of antihypertensive agents by step-wise discriminant analysis . Curr Med Res Opin. 1983;;8: 509-517.
Maland LJ, Lutz LJ, Castle CH.  Effects of withdrawing diuretic therapy on blood pressure in mild hypertension . Hypertension. 1983;;5:539-544.
Hansen AG, Jensen H, Langesen LP, Petersen A.  Withdrawal of antihypertensive drugs in the elderly . Acta Med Scand. 1983;;676( (suppl 2) ):178-185.
Alderman MH, Davis T, Gerber LM.  Systemic drug withdrawal to avoid unnecessary antihypertensive therapy . Abstract Volume of the International Society of Hypertension; 1984;:87.
Alderman MH, Davis T, Gerber LM, Robb M.  Antihypertensive drug therapy withdrawal in a general population . Arch Intern Med. 1986;;146: 1309-1311.
Jennings GL, Korner PI, Laufer E, Ester MD, Burton D, Bruce A.  How hypertension redevelops after cessation of long-term therapy . J Hypertens. 1984;;2( (suppl 3) ):217-219.
Langford HG.  Drug and dietary intervention in hypertension . Hypertension. 1982;;4( (suppl III) ): 166-169.
Langford HG, Blaufox MD, Oberman A, et al.  Dietary therapy slows the return of hypertension after stopping prolonged medication . JAMA. 1985;;253:657-664.
Blaufox MD, Langford HG, Oberman A, Hawkins CM, Wassertheil-Smooer S, Cutter GR.  Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH) . J Hypertens. 1984;;2( (suppl 3) ):179-181.
Langford HG, Blaufox MD, Oberman A, et al.  Does effective antihypertensive therapy partially 'cure' hypertension ? Trans Am Clin Climatol Assoc. 1984;;96:111-119.
Schmieder RE, Ruddel H, Neus H, Neus J, Von Eiff AW.  Predictors of blood pressure increases after withdrawal of antihypertensive therapy . J Hypertens. 1985;;3( (suppl 3) ):S457-S459.
Bahr M, Ruddel H, Schmieder R, Schulte W.  Langzeituntersuchungen nach Absetzen von Antihypertensiva bei Patienten mit milder Hypertonie . Med Welt. 1989;;40:1336-1338.
Horwitz D, Pettinger WA, Orvis H, Thomas RE, Sjoerdsma A.  Effects of methyldopa in 50 hypertensive patients . Clin Pharmacol Ther. 1967;;8:224-234.
Scott JN, McDevitt DG.  Rebound hypertension after acute methyldopa withdrawal . BMJ. 1976;;2:367.
Frewin DB, Penhall RK.  Rebound hypertension after sudden discontinuation of methyldopa therapy . Med J Aust. 1977;;1:659.
Garbus SB, Weber MA, Priest RT, Brewer DD, Hubbel FA.  The abrupt discontinuation of antihypertensive treatment . J Clin Pharmacol. 1979;;19:476-486.
Mancia G.  Methods for assessing blood pressure values in humans . Hypertension. 1983;;5( (suppl III) ):13.
Management Committee of the Australian Therapeutic Trial in Mild Hypertension.  Untreated mild hypertension . Lancet. 1982;;1:185-191.
PickeringTG, James GD, Boddie C, Harshfield GA, Blank S, Laragh JH.  How common is white coat hypertension ? JAMA. 1988;;259:225-228.
Management Committee of the Australian Therapeutic Trial in Mild Hypertension.  The Australian Therapeutic Trial in Mild Hypertension: report by the management committee . Lancet. 1980;;1:1261-1267.
Folkow B.  Physiological aspects of primary hypertension . Physiol Rev. 1982;;62:347-504.
Frohlich ED.  Hemodynamic factors in the pathogenesis and maintenance of hypertension . Fed Proc. 1982;;41:2400-2408.
Frohlich ED, Kozul VJ, Tarazi RC, Dustan HP.  Physiological comparison of labile and essential hypertension . Circ Res. 1970;;27( (suppl I) ):55-63.
Messerli FH, Frohlich ED, Suarez DH, et al.  Borderline hypertension: relationship between age, hemodynamics and circulating catecholamines . Circulation. 1981;;64:760-764.
Messerli FH, De Carvalho JGR, Christie B, Frohlich ED.  Systemic and regional hemodynamics in low, normal, and high cardiac output borderline hypertension . Circulation. 1978;;53:441-448.
Julius S, Pascual AV, Sannerstedt R, Mitchell C.  Relationship between cardiac output and peripheral resistance in borderline hypertension . Circulation. 1971;;43:382-390.
Julius S, Esler M, Randall OS, et al.  Neurogenic maintenance of peripheral resistance in borderline hypertension . Acta Physiol Lab Annu. 1974;;24:425-431.
Tanaka S, Takeshita A, Tomoike H, et al.  Role of autonomic and non-autonomic circulatory components in borderline hypertension in young men . Jpn Heart J. 1978;;19:66-73.
Freis ED.  Hemodynamics of hypertension . Physiol Rev. 1960;;40:27-53.
Folkow B.  The Fourth Volhard lecture: cardiovascular structural adaptation: its role in the initiation and maintenance of primary hypertension . Clin Sci Mol Med. 1978;;55( (suppl 4) ):3s-22s.
Folkow B, Grimby G, Thulesius O.  Adaptive structural changes of the vascular wall in hypertension and their relation to the control of peripheral resistance . Acta Physiol Scand. 1958;;44:255-272.
Korner PI, Bobik A, Angens JA, Adams MA, Friberg P.  Resistance control in hypertension . J Hypertens. 1989;;7( (suppl 4) ):S125-S134.
Perera GA.  Hypertensive vascular disease: description and natural history . J Chronic Dis. 1955;;1:33-42.
Kannei WB.  Prevalence and natural history of electrocardiographic left ventricular hypertrophy . Am J Med. 1983;;75( (suppl 3A) ):4-11.
Asmar RG, Pannier B, Jantoni JPH, et al.  Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension . Circulation. 1988;; 78:941-950.
Garavaglia GE, Messerli FH, Nunez BD, Schmieder R, Frohlich EE.  Angiotensin converting enzyme inhibitors: disparities in the mechanism of the antihypertensive effect . Am J Hypertens. 1988;;1:214-216.
Schmieder RE, Messerli FH, Garavaglia GE, Nunez BD.  Cardiovascular effects of verapamil in patients with essential hypertension . Circulation. 1987;;75:1030-1036.
Schmieder RE, Rueddel H, Neus H, Messerli FH, von Eiff AW.  Disparate hemodynamic response to mental challenge after antihypertensive therapy with beta blockers and calcium entry blockers . Am J Med. 1987;;82:11-16.
Christensen KL, Jespersen LT, Mulvany MJ.  Development of blood pressure in spontaneously hypertensive rats after withdrawal of long-term treatment related to vascular structure . J Hypertens. 1989;;7:83-90.
Adams MA, Bobik A, Korner PI.  Enalapril induced regression of vascular structure in spontaneously hypertensive rats attenuates redevelopment of blood pressure when treatment is withdrawn . J Hypertens. 1989;;7( (suppl 6) ):351. Abstract.
Sen S, Tarazi RC.  Regression of myocardial hypertrophy and influence of adrenergic system . Am J Physiol. 1983;;244:H97-H101.
Trimarco B, Wikstrand J.  Regression of cardiovascular structural changes by antihypertensive treatment: functional consequences and time course reversal judged from clinical studies . Hypertension . 1984;;6( (suppl III) ):150-157.
Tarazi RC.  Regression of left ventricular hypertrophy by medical treatment: present status and possible implications . Am J Med. 1983;;75:80-86.
Kannel WB, D'Agostini RB, Levy D, Belanger A J.  Prognostic significance of regression of left ventricular hypertrophy . Circulation. 1988;;78 ( (suppl II) ): 89. Abstract.
Dunn FG, Ventura HO, Messerli FH, Kobrin I, Frohlich EE.  Time course of regression of left ventricular hypertrophy in hypertensive patients treated with atenolol . Circulation. 1987;;76:254-258.
Schmieder RE, Messerli FH, Sturgill D, Garavaglia GE, Nunez BD.  Cardiac performance after reduction of myocardial hypertrophy . Am J Med. 1989;;87:22-27.
Trimarco B, De Luca N, Ricciardelli B, et al.  Cardiac function in systemic hypertension before and after reversal of left ventricular hypertrophy . Am J Cardiol. 1988;;62:745-750.
Spech MM, Ferrario CM, Tarazi RC.  Cardiac pumping ability following reversal of hypertrophy and hypertension in spontaneously hypertensive rats . Hypertension. 1980;;2:75-82.
Inouye I, Massie B, Lije D, et al.  Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension . Am J Cardiol. 1984;; 53:120-126.
Smith V-E, Katz AM.  Left ventricular relaxation in hypertension . In: Messerli FH, ed. The Heart and Hypertension . New York, NY: Yorke Medical Books; 1987;:143-152.
Trimarco B, De Luca N, Rosiello G, et al.  Reversal of left ventricular hypertrophy improves diastolic function in hypertension . Circulation. 1988;;78( (suppl II) ):64. Abstract.
Tubau JF, Szlachcic J, Massie BM, Hendersson S, Volmer C.  Improvement of diastolic filling following hypertrophy reversal . J Am Coll Cardiol. 1986;;7:112A. Abstract.
Fletcher AE, Franks PJ, Bulpitt CJ.  The effect of withdrawing antihypertensive therapy: a review . J Hypertens. 1988;;6:431-436.
Shaper AG, Wannamethee G, Whincup P.  Alcohol and blood pressure in middle-aged British men . J Hum Hypertens. 1988;;2:71-78.
Keys A, Taylor HL, Blackburn H, Brozek J, Anderson JT, Simonson E.  Mortality and coronary heart disease among men studied for 23 years . Arch Intern Med. 1971;;128:201-210.

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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.
Helgeland A.  Treatment of mild hypertension: a 5 year controlled drug trial: the Oslo study . Am J Med. 1980;;69:725-732.
Hypertension Detection and Follow-up Program Cooperative Group.  Five year findings of the Hypertension Detection and Follow-up Program, I: reduction in mortality of persons with high blood pressure, including mild hypertension . JAMA. 1979;;242:2562-2571.
European Working Party on High Blood Pressure in the Elderly.  Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial . Lancet. 1985;;1:1349-1354.
 Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results . BMJ. 1985;;291:97-104.
MacMahon SW, Cutter JA, Neaton JD, Payne GH.  Relationship of blood pressure to coronary and stroke morbidity and mortality in clinical trials and epidemiological studies . J Hypertens. 1986;;4( (suppl 6) ):14-17.
Cruickshank JM.  Why has the primary prevention of myocardial infarction in the treatment of hypertension been so elusive ? J Hum Hypertens. 1987;;1:73-81.
Beckenridge A.  Compliance of hypertensive patients with pharmacological treatment . Hypertension. 1983;;5( (suppl III) ):85-89.
Multiple Risk Factor Intervention Trial Research Group.  Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial . Am J Cardiol. 1985;;55:1-15.
Hollifield JW.  Potassium and magnesium abnormalities: diuretics and arrhythmias in hypertension . Am J Med. 1984;;77( (suppl 5A) ):28-32.
Grimm RH Jr, Leon AS, Hunninghake DB, Lenz K, Hannan P, Blackburn H.  Effects of thiazide diuretics on plasma lipids and lipoproteins in mildly hypertensive patients: a double-blind controlled trial . Ann Intern Med. 1981;;94:7-11.
Finnerty FA Jr.  Step-down treatment of mild systemic hypertension . Am J Cardiol. 1984;;53: 1304-1307.
 Veterans Administration Cooperative Study Group on Antihypertensive Agents. Return of elevated blood pressure after withdrawal of antihypertensive drugs . Circulation. 1975;;51:1107-1113.
Stamler R, Stamler J, Grimm R, et al.  Trial on control of hypertension by nutritional means: three-year results . J Hypertens. 1984;;2( (suppl 3) ):167-170.
 Medical Research Council Working Party on Mild Hypertension. Course of blood pressure in mild hypertensives after withdrawal of long term antihypertensive treatment . BMJ. 1986;;293:988-992.
Stamler R, Stamler J, Grimm R, et al.  Nutritional therapy for high blood pressure: final report of a 4-year randomized controlled trial—The Hypertension Control Program . JAMA. 1987;;257: 1484-1491.
Freis ED, Thomas JR, Fisher SG, et al.  Effects of reduction in drugs or dosage after long-term control of systemic hypertension . Am J Cardiol. 1989;;63:702-708.
Zanchetti A.  Treatment goals in hypertension . Am J Med. 1984;;76:1-3.
The Joint National Committee on Detection,  Evaluation, and Treatment of High Blood Pressure. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure . Arch Intern Med. 1988;;148: 1023-1038.
Page IH, Dustan HP.  Persistence of normal blood pressure after discontinuing treatment in hypertensive patients . Circulation. 1962;;25:433-436.
Perry HM Jr, Schroeder HA, Catanzaro FJ, Moore-Jones D.  Studies on the control of hypertension, VIII: mortality, morbidity, and remissions during 12 years of intensive therapy . Circulation. 1966;;33:958-972.
Thurm RH, Smith WM.  On resetting of'barostats' in hypertensive patients . JAMA. 1967;;201: 301-304.
Dustan HP, Page IH, Tarazi RC, Frohlich ED.  Arterial pressure responses to discontinuing antihypertensive drugs . Circulation. 1968;;37:370-379.
Boyle RM, Price ML, Hamilton M.  Thiazide withdrawal in hypertension . J R Coll Physicians Lond. 1979;;13:172-173.
Levinson PD, Khatri IM, Freis ED.  Persistence of normal BP after withdrawal of drug treatment in mild hypertension . Arch Intern Med. 1982;;142:2265-2268.
Fernandez PG, Kim BK, Galway AB, Sharma JN.  Separation of essential hypertensive patients based on blood pressure responses after the withdrawal of antihypertensive agents by step-wise discriminant analysis . Curr Med Res Opin. 1983;;8: 509-517.
Maland LJ, Lutz LJ, Castle CH.  Effects of withdrawing diuretic therapy on blood pressure in mild hypertension . Hypertension. 1983;;5:539-544.
Hansen AG, Jensen H, Langesen LP, Petersen A.  Withdrawal of antihypertensive drugs in the elderly . Acta Med Scand. 1983;;676( (suppl 2) ):178-185.
Alderman MH, Davis T, Gerber LM.  Systemic drug withdrawal to avoid unnecessary antihypertensive therapy . Abstract Volume of the International Society of Hypertension; 1984;:87.
Alderman MH, Davis T, Gerber LM, Robb M.  Antihypertensive drug therapy withdrawal in a general population . Arch Intern Med. 1986;;146: 1309-1311.
Jennings GL, Korner PI, Laufer E, Ester MD, Burton D, Bruce A.  How hypertension redevelops after cessation of long-term therapy . J Hypertens. 1984;;2( (suppl 3) ):217-219.
Langford HG.  Drug and dietary intervention in hypertension . Hypertension. 1982;;4( (suppl III) ): 166-169.
Langford HG, Blaufox MD, Oberman A, et al.  Dietary therapy slows the return of hypertension after stopping prolonged medication . JAMA. 1985;;253:657-664.
Blaufox MD, Langford HG, Oberman A, Hawkins CM, Wassertheil-Smooer S, Cutter GR.  Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH) . J Hypertens. 1984;;2( (suppl 3) ):179-181.
Langford HG, Blaufox MD, Oberman A, et al.  Does effective antihypertensive therapy partially 'cure' hypertension ? Trans Am Clin Climatol Assoc. 1984;;96:111-119.
Schmieder RE, Ruddel H, Neus H, Neus J, Von Eiff AW.  Predictors of blood pressure increases after withdrawal of antihypertensive therapy . J Hypertens. 1985;;3( (suppl 3) ):S457-S459.
Bahr M, Ruddel H, Schmieder R, Schulte W.  Langzeituntersuchungen nach Absetzen von Antihypertensiva bei Patienten mit milder Hypertonie . Med Welt. 1989;;40:1336-1338.
Horwitz D, Pettinger WA, Orvis H, Thomas RE, Sjoerdsma A.  Effects of methyldopa in 50 hypertensive patients . Clin Pharmacol Ther. 1967;;8:224-234.
Scott JN, McDevitt DG.  Rebound hypertension after acute methyldopa withdrawal . BMJ. 1976;;2:367.
Frewin DB, Penhall RK.  Rebound hypertension after sudden discontinuation of methyldopa therapy . Med J Aust. 1977;;1:659.
Garbus SB, Weber MA, Priest RT, Brewer DD, Hubbel FA.  The abrupt discontinuation of antihypertensive treatment . J Clin Pharmacol. 1979;;19:476-486.
Mancia G.  Methods for assessing blood pressure values in humans . Hypertension. 1983;;5( (suppl III) ):13.
Management Committee of the Australian Therapeutic Trial in Mild Hypertension.  Untreated mild hypertension . Lancet. 1982;;1:185-191.
PickeringTG, James GD, Boddie C, Harshfield GA, Blank S, Laragh JH.  How common is white coat hypertension ? JAMA. 1988;;259:225-228.
Management Committee of the Australian Therapeutic Trial in Mild Hypertension.  The Australian Therapeutic Trial in Mild Hypertension: report by the management committee . Lancet. 1980;;1:1261-1267.
Folkow B.  Physiological aspects of primary hypertension . Physiol Rev. 1982;;62:347-504.
Frohlich ED.  Hemodynamic factors in the pathogenesis and maintenance of hypertension . Fed Proc. 1982;;41:2400-2408.
Frohlich ED, Kozul VJ, Tarazi RC, Dustan HP.  Physiological comparison of labile and essential hypertension . Circ Res. 1970;;27( (suppl I) ):55-63.
Messerli FH, Frohlich ED, Suarez DH, et al.  Borderline hypertension: relationship between age, hemodynamics and circulating catecholamines . Circulation. 1981;;64:760-764.
Messerli FH, De Carvalho JGR, Christie B, Frohlich ED.  Systemic and regional hemodynamics in low, normal, and high cardiac output borderline hypertension . Circulation. 1978;;53:441-448.
Julius S, Pascual AV, Sannerstedt R, Mitchell C.  Relationship between cardiac output and peripheral resistance in borderline hypertension . Circulation. 1971;;43:382-390.
Julius S, Esler M, Randall OS, et al.  Neurogenic maintenance of peripheral resistance in borderline hypertension . Acta Physiol Lab Annu. 1974;;24:425-431.
Tanaka S, Takeshita A, Tomoike H, et al.  Role of autonomic and non-autonomic circulatory components in borderline hypertension in young men . Jpn Heart J. 1978;;19:66-73.
Freis ED.  Hemodynamics of hypertension . Physiol Rev. 1960;;40:27-53.
Folkow B.  The Fourth Volhard lecture: cardiovascular structural adaptation: its role in the initiation and maintenance of primary hypertension . Clin Sci Mol Med. 1978;;55( (suppl 4) ):3s-22s.
Folkow B, Grimby G, Thulesius O.  Adaptive structural changes of the vascular wall in hypertension and their relation to the control of peripheral resistance . Acta Physiol Scand. 1958;;44:255-272.
Korner PI, Bobik A, Angens JA, Adams MA, Friberg P.  Resistance control in hypertension . J Hypertens. 1989;;7( (suppl 4) ):S125-S134.
Perera GA.  Hypertensive vascular disease: description and natural history . J Chronic Dis. 1955;;1:33-42.
Kannei WB.  Prevalence and natural history of electrocardiographic left ventricular hypertrophy . Am J Med. 1983;;75( (suppl 3A) ):4-11.
Asmar RG, Pannier B, Jantoni JPH, et al.  Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension . Circulation. 1988;; 78:941-950.
Garavaglia GE, Messerli FH, Nunez BD, Schmieder R, Frohlich EE.  Angiotensin converting enzyme inhibitors: disparities in the mechanism of the antihypertensive effect . Am J Hypertens. 1988;;1:214-216.
Schmieder RE, Messerli FH, Garavaglia GE, Nunez BD.  Cardiovascular effects of verapamil in patients with essential hypertension . Circulation. 1987;;75:1030-1036.
Schmieder RE, Rueddel H, Neus H, Messerli FH, von Eiff AW.  Disparate hemodynamic response to mental challenge after antihypertensive therapy with beta blockers and calcium entry blockers . Am J Med. 1987;;82:11-16.
Christensen KL, Jespersen LT, Mulvany MJ.  Development of blood pressure in spontaneously hypertensive rats after withdrawal of long-term treatment related to vascular structure . J Hypertens. 1989;;7:83-90.
Adams MA, Bobik A, Korner PI.  Enalapril induced regression of vascular structure in spontaneously hypertensive rats attenuates redevelopment of blood pressure when treatment is withdrawn . J Hypertens. 1989;;7( (suppl 6) ):351. Abstract.
Sen S, Tarazi RC.  Regression of myocardial hypertrophy and influence of adrenergic system . Am J Physiol. 1983;;244:H97-H101.
Trimarco B, Wikstrand J.  Regression of cardiovascular structural changes by antihypertensive treatment: functional consequences and time course reversal judged from clinical studies . Hypertension . 1984;;6( (suppl III) ):150-157.
Tarazi RC.  Regression of left ventricular hypertrophy by medical treatment: present status and possible implications . Am J Med. 1983;;75:80-86.
Kannel WB, D'Agostini RB, Levy D, Belanger A J.  Prognostic significance of regression of left ventricular hypertrophy . Circulation. 1988;;78 ( (suppl II) ): 89. Abstract.
Dunn FG, Ventura HO, Messerli FH, Kobrin I, Frohlich EE.  Time course of regression of left ventricular hypertrophy in hypertensive patients treated with atenolol . Circulation. 1987;;76:254-258.
Schmieder RE, Messerli FH, Sturgill D, Garavaglia GE, Nunez BD.  Cardiac performance after reduction of myocardial hypertrophy . Am J Med. 1989;;87:22-27.
Trimarco B, De Luca N, Ricciardelli B, et al.  Cardiac function in systemic hypertension before and after reversal of left ventricular hypertrophy . Am J Cardiol. 1988;;62:745-750.
Spech MM, Ferrario CM, Tarazi RC.  Cardiac pumping ability following reversal of hypertrophy and hypertension in spontaneously hypertensive rats . Hypertension. 1980;;2:75-82.
Inouye I, Massie B, Lije D, et al.  Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension . Am J Cardiol. 1984;; 53:120-126.
Smith V-E, Katz AM.  Left ventricular relaxation in hypertension . In: Messerli FH, ed. The Heart and Hypertension . New York, NY: Yorke Medical Books; 1987;:143-152.
Trimarco B, De Luca N, Rosiello G, et al.  Reversal of left ventricular hypertrophy improves diastolic function in hypertension . Circulation. 1988;;78( (suppl II) ):64. Abstract.
Tubau JF, Szlachcic J, Massie BM, Hendersson S, Volmer C.  Improvement of diastolic filling following hypertrophy reversal . J Am Coll Cardiol. 1986;;7:112A. Abstract.
Fletcher AE, Franks PJ, Bulpitt CJ.  The effect of withdrawing antihypertensive therapy: a review . J Hypertens. 1988;;6:431-436.
Shaper AG, Wannamethee G, Whincup P.  Alcohol and blood pressure in middle-aged British men . J Hum Hypertens. 1988;;2:71-78.
Keys A, Taylor HL, Blackburn H, Brozek J, Anderson JT, Simonson E.  Mortality and coronary heart disease among men studied for 23 years . Arch Intern Med. 1971;;128:201-210.
CME Course for:


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To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
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