Abstract
High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the α1-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy. The add-on effects of doxazosin at the maximum dose of 6 mg at bedtime on home blood pressure and left ventricular geometry for 1 year were investigated in 49 subjects (37 men and 12 women, aged 57.5±9.1 years) with morning hypertension who had been treated with amlodipine alone for more than 1 year. Doxazosin induced a significant decrease in morning blood pressure (145.6±5.6/91.5±5.4 to 132.4±3.7/83.6±5.6 mmHg, p≤0.001/<0.001) without a change of evening blood pressure (128.9±5.1/79.8±5.1 to 127.7±6.0/78.8±6.2 mmHg, p=0.056/0.051). Left ventricular mass index (LVMI; 124.8±19.8 to 95.6±15.7 g/m2, p<0.001), relative wall thickness (0.457±0.061 to 0.405±0.047, p<0.001) and homeostasis model assessment of the insulin resistance index (HOMA-IR; 2.62±1.43 to 1.33±0.75, p<0.001) were decreased after doxazosin therapy. A stepwise multivariate regression analysis revealed that the changes in morning systolic blood pressure (adjusted r2=34.9%, p<0.001) and HOMA-IR (adjusted r2=4.5%, p=0.046) were significant contributory factors to the change in LVMI after doxazosin therapy. These results suggest that bedtime dosing of doxazosin is useful for the control of morning blood pressure and regression of left ventricular hypertrophy.
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Muller JE : Circadian variation in cardiovascular events. Am J Hypertens 1999; 12: 35S–42S.
Elliot WJ : Cyclic and circadian variations in cardiovascular events. Am J Hypertens 2001; 14: 291S–295S.
Leary AC, Struthers AD, Donnan PT, MacDonald TM, Murphy MB : The morning surge in blood pressure and heart rate is dependent on levels of physical activity after waking. J Hypertens 2002; 20: 865–870.
Gosse P, Ansoborlo P, Lemetayer P, Clementy J : Left ventricular mass is better correlated with arising blood pressure than with office or occasional blood pressure. Am J Hypertens 1997; 10: 505–510.
Imai Y, Ohkubo T, Tsuji I, et al: Prognostic value of ambulatory and home blood pressure measurements in comparison to screening blood pressure measurements: a pilot study in Ohasama. Blood Press Monit 1996; 1: S51–S58.
Gosse P, Cipriano C, Bemurat L, et al: Prognostic significance of blood pressure measured on rising. J Hum Hypertens 2001; 15: 413–417.
Kario K, Ishikawa J, Pickering TG, et al: Morning hypertension: the strongest independent risk factor for stroke in elderly hypertensive patients. Hypertens Res 2006; 29: 581–587.
Poirier L, Lefebvre J, Lacourciere Y : Chronotherapeutics: are there meaningful difference among antihypertensive drugs? Curr Hypertens Rep 1999; 1: 320–327.
White WB, LaRocca GM : Chronopharmacology of cardiovascular therapy. Blood Press Monit 2002; 7: 199–207.
Klingbeil AU, Schneider M, Martus P, Messerli FH, Schmieder RE : A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med 2003; 115: 41–46.
Neutel JM, Smith DHG, Weber MA : Effect of antihypertensive monotherapy and combination therapy on arterial distensibility and left ventricular mass. Am J Hypertens 2004; 17: 37–42.
Yamamoto Y, Sonoyama K, Matsubara K, et al: The status of hypertension management in Japan in 2000. Hypertens Res 2002; 25: 717–725.
Mori H, Ukai H, Yamamoto H, et al: Current status of antihypertensive prescription and associated blood pressure control in Japan. Hypertens Res 2006; 29: 143–151.
Chobanian AV, Bakris GL, Black HR, et al, the National High Blood Pressure Education Program Coordinating Committee : Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206–1252.
Guidelines Committee : 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–1053.
World Health Organization, International Society of Hypertension Writing Group: 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003; 21: 1983–1992.
Williams B, Poulter NR, Brown MJ, et al: Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Hum Hypertens 2004; 18: 139–185.
Darnis F, Poupon R : Pharmacokinetics and safety of single oral doses of amlodipine in patients with and without hepatic impairment: an open study. Int J Clin Pharm Res 1993; 13: 29–33.
Ishimitsu T, Minami J, Kawano Y, Numabe A, Takishita S, Matsuoka H : Amlodipine, a long-acting calcium channel blocker, attenuates morning blood pressure rise in hypertensive patients. Clin Exp Pharmacol Physiol 1999; 26: 500–504.
Lorimer AR, Lyons D, Fowler G, Petrie JC, Rothman MT : Differences between amlodipine and lisinopril in control of clinic and twenty-four hour ambulatory blood pressures. J Hum Hypertens 1998; 12: 411–416.
Ikeda T, Gomi T, Shibuya Y, et al: Morning rise in blood pressure is a predictor of left ventricular hypertrophy in treated hypertensive patients. Hypertens Res 2004; 27: 939–946.
White WB, Anwar YA : Evaluation of the overall efficacy of the Omron office digital blood pressure HEM-907 monitor in adults. Blood Press Monit 2001; 6: 107–110.
Imai Y, Otsuka K, Kawano Y, et al: Japanese Society of Hypertension (JSH) guidelines for self-monitoring of blood pressure at home. Hypertens Res 2003; 26: 771–782.
Sahn DJ, DeMaria A, Kisslo J, Weyman A : Recommendations regarding quantitation in M-mode echocardiography: result of a survey of echocardiographic measurements. Circulation 1978; 58: 1072–1083.
Devereux RB, Alonso DR, Lutas EM, et al: Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57: 450–458.
Reichek N, Devereux RB : Reliable estimation of peak left ventricular systolic pressure by M-mode echographic-determined end-diastolic relative wall thickness: identification of severe valvular aortic stenosis in adult patients. Am Heart J 1982; 103: 202–209.
Techholz LE, Kreulen T, Herman MV, Gorlin R : Problems in echocardiographic volume determinations: echocardiographic-angiographic correlation in the presence or absence of asynergy. Am J Cardiol 1976: 37; 7–11.
Wallerson DC, Ganau A, Roman MJ, Devereux RB : Measurement of cardiac output by M-mode and two-dimentinal echocardiography: application to patients with hypertension. Eur Heart J 1990: 11 ( Suppl I); 67–78.
Zoghbi WA, Enriquez-Sarano M, Foster E, et al: Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003; 16: 777–802.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC : Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.
Pickering TG, Levenstein M, Walmsley P, for the Hypertension and Lipid Trial Study Group: Nighttime dosing of doxazosin has peak effect on morning ambulatory blood pressure: results of the HALT Study. Am J Hypertens 1994; 7: 844–847.
Kario K, Pickering TG, Hoshide S, et al: Morning blood pressure surge and hypertensive cerebrovascular disease. Am J Hypertens 2004; 17: 668–675.
Stergiou GS, Baibas NM, Gantzarou AP, et al: Reproducibility of home, ambulatory, and clinic blood pressure: implications for the design of trials for the assessment o antihypertensive drug efficacy. Am J Hypertens 2002; 15: 101–104.
de Champlain, Karas M, Nguyen P, et al: Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients. J Hypertens 1998; 16: 1357–1369.
Kamoi K, Ikarashi T : The bedtime administration of doxazosin controls morning hypertension and albuminuria in patients with type-2 diabetes: evaluation using home-based blood pressure measurements. Clin Exp Hypertens 2005; 4: 369–376.
Stafford RS, Furberg CD, Finkelstein SN, Cockburn IM, Alehegn T, Ma J : Impact of clinical trial results on national trends in α-blocker prescribing, 1996–2002. JAMA 2004; 291: 54–62.
The ALLHAT Office and Coordinators for the ALLHAT Collaborative Research Group: Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2000; 283: 1967–1975.
Rutter MK, Parise H, Benjamin EJ, et al: Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study. Circulation 2003; 107: 448–454.
Verdecchia P, Reboldi G, Schillaci G, et al: Circulating insulin and insulin growth factor-1 are independent determinants of left ventricular mass and geometry in essential hypertension. Circulation 1999; 100: 1802–1807.
Andersson PE, Lithell H : Metabolic effects of doxazosin and enalapril in hypertriglycemic, hypertensive men. Am J Hypertens 1996; 9: 323–333.
Lender D, Arauz-Pacheco C, Breen L, Mora-Mora P, Ramirez LC, Raskin P : A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients. Am J Hypertens 1999; 12: 298–303.
de Courten M, Ferrari P, Schneider M, et al: Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension. Eur J Clin Pharmacol 1993; 44: 457–462.
Grim RG, Flank JM, Granditis GA, et al: Long-term effects on plasma lipids on diet and drugs to treated hypertension. JAMA 1996; 275: 1549–1556.
Levy D, Walmsley P, Levenstein M, for the Hypertension and Lipid Trial Srusy Group: Principal results on the Hypertension and Lipid Trial (HALT): a multicenter study of doxazosin in patients with hypertension. Am Heart J 1996; 131: 966–973.
Ishimitsu T, Yagi S, Sugishita Y, et al: Long-term effects of doxazosin, an alpha1-blocker, on serum lipids in hypertensive patients. Hypertnes Res 1996; 19: 43–49.
Marshall HG, Beevers DG : α-Adrenoceptor blocking drugs and female urinary incontinence: prevalence and reversibility. Br J Clin Pharmacol 1996; 42: 507–509.
Messerli FH : Vasodilatory edema: a common side effect of antihypertensive therapy. Curr Cardiol Rep 2002; 4: 479–482.
Hashimoto J, Chonan K, Aoki Y, et al: Therapeutic effects of evening administration of guanabenz and clonidine on morning hypertension: evaluation using home-based blood pressure measurements. J Hypertens 2003; 23: 805–811.
Gosse P, Jullien V, Jarneir P, Lametayer P, Clementy J : Echocardiographic definition of left ventricular hypertrophy in the hypertensive: which methods of indexation of left ventricular mass? J Hum Hypertens 1999; 13: 505–509.
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Ikeda, T., Gomi, T., Shibuya, Y. et al. Add-On Effect of Bedtime Dosing of the α1-Adrenergic Receptor Antagonist Doxazosin on Morning Hypertension and Left Ventricular Hypertrophy in Patients Undergoing Long-Term Amlodipine Monotherapy. Hypertens Res 30, 1097–1105 (2007). https://doi.org/10.1291/hypres.30.1097
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DOI: https://doi.org/10.1291/hypres.30.1097