Aktuelle Kardiologie 2013; 2(3): 183-188
DOI: 10.1055/s-0032-1328503
Übersichtsarbeit
Georg Thieme Verlag KG Stuttgart · New York

Chronopathologie der Hypertonie und antihypertensive Chronotherapie

Chronopathology of Hypertension and Antihypertensive Chronotherapy
Martin Middeke
Hypertoniezentrum München HZM, München
› Author Affiliations
Further Information

Publication History

Publication Date:
11 June 2013 (online)

Zusammenfassung

Die Chronopathologie der Hypertonie beschreibt die verschiedenen Phänomene der Normabweichung im zeitlichen Verlauf der Blutdruckregulation, ihre Charakteristika, die Ursachen, die diagnostische und prognostische Bedeutung, sowie die therapeutischen Konsequenzen. Dabei sind der nächtliche Blutdruck und der Tag-Nacht-Rhythmus von besonderem Interesse. In diesem Zusammenhang sind die chronopharmakologischen Aspekte der Antihypertensiva, d. h. die Berücksichtigung von Pharmakokinetik und -dynamik in Abhängigkeit von der Tageszeit, der Applikation und der Wirkdauer der Substanz von großer klinischer Bedeutung.

Insbesondere eine nächtliche Blutdrucksenkung und die Wiederherstellung eines normalen zirkadianen Rhythmus sind wichtige Therapieziele bei Risikopatienten mit unzureichender Nachtabsenkung (non-dipper) oder einer Inversion des Blutdruckrhythmus (inverted dipper). Andererseits verbietet sich eine abendliche Dosierung bei Patienten mit spontan ausgeprägter nächtlicher Blutdrucksenkung (extreme dipper), um nächtliche Ischämien zu vermeiden. Dies gilt insbesondere für ältere Patienten und für Patienten mit kardiovaskulären Erkrankungen. Bei diesen Patienten sind eine individuelle Steuerung der antihypertensiven Medikation und eine Anpassung der Dosierungsintervalle nur mittels ABDM möglich. Dieses Vorgehen beschreibt die antihypertensive Chronotherapie.

Abstract

Chronopathology of hypertension describes deviations in blood pressure over time together with the characteristics, causes, and diagnostic and prognostic aspects of these deviations, and the implications for antihypertensive therapy. Nocturnal blood pressure and the circadian rhythm of blood pressure are of particular interest. Chronopharmacological aspects of antihypertensive medication, i. e. the changes in pharmacokinetics and -dynamics depending on the time of day, the administration of medication and the duration of its effectiveness, are clinically very important.

Ensuring a nocturnal fall in blood pressure and re-establishing a normal circadian rhythm are important therapeutic goals for high risk patients with an insufficient nocturnal drop in blood pressure (non-dipper) or an inversion of blood pressure rhythm (inverted dipper). In contrast, to prevent nocturnal ischemia, evening dosing of antihypertensive medication is contraindicated in patients with an extreme nocturnal fall in blood pressure (extreme dipper). This is particularly relevant for elderly patients and for patients with cardiovascular disease. Antihypertensive chronotherapy is indicated in these patients, i.e., the individual guidance of antihypertensive medication and adjustment of dosing intervals to take account of the circadian rhythm using ambulatory blood pressure monitoring (ABPM).

 
  • Literatur

  • 1 Middeke M. Blutdruckvariabilität: Diagnostik, prognostische Bedeutung und therapeutische Konsequenzen. Dtsch Med Wochenschr 2011; 136: 2361-2366
  • 2 Middeke M. Effect of nocturnal blood pressure measurement on sleep and blood pressure during sleep. Z Kardiol 1996; 85 (Suppl. 03) 99-105
  • 3 Anlauf M, Baumgart P, Krönig B et al. Statement zur „24-Stunden-Blutdruckmessung“ der Deutschen Liga zur Bekämpfung des hohen Blutdruckes. Z Kardiol 1991; 80 (Suppl. 01) 53-55
  • 4 Anlauf M, Baumgart P, Krönig B et al. Statement on ambulatory blood pressure monitoring by the German Hypertension League. Blood Pressure Measurement Section of the Deutsche Liga zur Bekämpfung des hohen Blutdruckes. J Hum Hypertens 1995; 9: 777-779
  • 5 Knudsen ST, Laugesen E, Hansen KW et al. Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients. Diabetologia 2009; 52: 698-704
  • 6 Middeke M, Mika E, Schreiber MA et al. Ambulante indirekte Blutdrucklangzeitmessung bei primärer und sekundärer Hypertonie. Klin Wochenschr 1989; 67: 713-716
  • 7 Middeke M, Schrader J. Nocturnal blood pressure in normotensive subjects and those with white coat, primary, and secondary hypertension. BMJ 1994; 308: 630-632
  • 8 Verdecchia P, Angeli F, Mazzotta G et al. Day-night dip and early morning surge in blood pressure in hypertension: prognostic implications. Hypertension 2012; 60: 34-42
  • 9 Middeke M. Drug effects on blood pressure rhythm in secondary hypertension. Annals NY Academy of Science 1996; 783: 270-277
  • 10 Burnier M, Coltamai L, Maillard M et al. Renal sodium handling and nightime blood pressure. Semin Nephrol 2007; 27: 565-571
  • 11 Uzu T, Takeji M, Yamauchi A et al. Circadian rhythm and postural change in natriuresis in non-dipper type of essential hypertension. J Hum Hypertens 2001; 15: 323-327
  • 12 Davidson MB, Hix JK, Vidt DG et al. Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate. Arch Intern Med 2006; 166: 846-852
  • 13 Astrup AS, Nielsen FS, Rossing P et al. Predictors of mortality in patients with type 2 diabetes with or without diabetic nephropathy: a follow-up study. J Hypertens 2007; 25: 2479-2485
  • 14 Farmer CK, Goldsmith DJ, Quin JD et al. Progression of diabetic nephropathy – is diurnal blood pressure rhythm as important as absolute blood pressure level?. Nephrol Dial Transplant 1998; 13: 635-639
  • 15 Palmas W, Pickering T, Teresi J et al. Nocturnal blood pressure elevation predicts progression of albuminuria in elderly people with type 2 diabetes. J Clin Hypertens 2008; 10: 12-20
  • 16 Dolan E, Stanton A, Thijs L et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension 2005; 46: 156-161
  • 17 Boggia J, Thijs L, Hansen TW et al. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet 2007; 370: 1219-1229
  • 18 Fagard RH, Celis H, Thijs L et al. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension 2008; 51: 55-61
  • 19 Hoshide Y, Kario K, Schwartz JE et al. Incomplete benefit of antihypertensive therapy on stroke reduction in older hypertensives with abnormal nocturnal blood pressure dipping (extreme-dippers and reverse-dippers). Am J Hypertens 2002; 15: 844-850
  • 20 Kario K, Matsuo T, Kobayashi H et al. Nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensive patients. Advanced silent cerebrovascular damage in extreme dippers. Hypertension 1996; 27: 130-135
  • 21 Ohkubo T, Imai Y, Tsuji I et al. Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in Ohasama. J Hypertens 1997; 15: 357-364
  • 22 Pierdomenico D, Bucci A, Costantini F et al. Circadian blood pressure changes and myocardial ischemia in hypertensive patients with coronary artery disease. J Am Coll Cardiol 1998; 31: 1627-1634
  • 23 Kario K, Pickering TG, Umeda Y et al. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives. A prospective Study. Circulation 2003; 107: 1401-1406
  • 24 Portaluppi F, Vergnani L, Manfredini R et al. Time-dependent effect of isradipine on the nocturnal hypertension in chronic renal failure. Am J Hypertens 1995; 8: 719-726
  • 25 Hermida RC, Ayala DE, Mojon A et al. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int 2010; 27: 1629-1651
  • 26 Middeke M, von Bielinski C. Antihypertensive chronotherapy in diabetes. J Hypertens 2008; 26 (Suppl. 01) S208
  • 27 Kario K, Pickering T, Matsuo T et al. Stroke prognosis and abnormal nocturnal blood pressure fall in older hypertensives. Hypertension 2001; 38: 852-857
  • 28 Middeke M. Die U-förmige Beziehung zwischen nächtlichem Blutdruck und Organschäden. Dtsch Med Wochenschr 2005; 130: 2640-2642
  • 29 Lemmer B. The importance of circadian rhythms on drug response in hypertension and coronary heart disease–from mice and man. Pharmacol Ther 2006; 111: 629-651
  • 30 Middeke M, Klüglich M, Holzgreve H. Chronopharmacology of captopril plus hydrochlorothiazide in hypertension: morning versus evening dosing. Chronobiol Int 1991; 8: 506-510