Antihypertensive Chronotherapie Chronopathologie renaler Hochdruckformen

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. Bei der renalen Hypertonie sind der nächtliche Blutdruck und der Tag-Nacht-Rhythmus von besonderem Interesse. Daher sind die chronopharmakologischen Aspekte der antihypertensiven Therapie, also die Berücksichtigung von Pharmakokinetik und -dynamik in Abhängigkeit von der Tageszeit, der Applikation und der Wirkdauer der Substanzen, von großer klinischer Bedeutung bei Patienten mit renalen Hochdruckformen. 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 Blutdruckabsenkung („super 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 ambulanter Blutdrucklangzeitmessung möglich. Dieses Vorgehen beschreibt die antihypertensive Chronotherapie.

The chronopathology of hypertension describes the variations in the course of blood pressure regulation over time, their nature, causes, diagnostic and prognostic significance and therapeutic consequences. In renal hypertension, nocturnal blood pressure and the day/night rhythm are of particular interest. For this reason, the chronopharmacological aspects of antihypertensive treatment – that is, the consideration of the pharmacokinetics and -dynamics during the course of the day, the application and duration of effect of medications – are of considerable clinical significance in patients with renal forms of hypertension. Important therapeutic aims in high-risk patients with inadequate nocturnal blood pressure drop (“non-dippers”) or inversion of the blood pressure rhythm (“inverted dippers”) are nocturnal decrease in blood pressure and the establishment of a normal circadian rhythm. However, to avoid nightly ischaemia, evening medication in patients experiencing marked spontaneous blood pressure drop (“super dipper”) is inadmissible. This applies in particular to elderly patients and to those with cardiovascular disease. Here, individual management of antihypertensive medication, and the regulation of administration intervals is possible only via ambulatory blood pressure measurement. This approach is described as antihypertensive chronotherapy.

Key words

hypertension - chronotherapy - chronopharmacology - blood pressure rhythm

Literatur

• 1 Fugiwara T, Kawamura M, Nakajima J et al.. Seasonal differences in diurnal blood pressure of hypertensive patients living in a stable environmental temperature.  J Hypertens. 1995;  13 1747-1752
• 2 Middeke M.. Das Blutdruck-Tagesprofil.  Münch Med Wochenschr. 1990;  132 568-570
• 3 Gemelli M, Manganaro R, Mami C et al.. Circadian blood pressure pattern in full-term newborn infants.  Biol Neonate. 1989;  56 315-323
• 4 Zadek I.. Die Messung des Blutdrucks am Menschen mittels des Baschschen Apparates.  Z Klin Med. 1881;  2 509-551
• 5 Hill L, Lond MB.. On rest, sleep, and work and the concomitant changes in the circulation of the blood.  Lancet. 1899;  1 282
• 6 Howell WHA.. Contribution to the physiology of sleep, based on plethysmographic experiments.  J exp Med. 1897;  2 313
• 7 Katsch G, Pansdorf H.. Die Schlafbewegung des Blutdrucks.  Münch Med Wochenschr. 1922;  69 1715-1718
• 8 Middeke M, Mika E, Schreiber MA et al.. Ambulante indirekte Blutdrucklangzeitmessung bei primärer und sekundärer Hypertonie.  Klin Wochenschr. 1989;  67 713-716
• 9 Middeke M, Schrader J.. Nocturnal blood pressure in normotensive subjects and those with white coat, primary, and secondary hypertension.  BMJ. 1994;  308 630-632
• 10 Scholze A, Burkert A, Mardanzai K et al.. Increased arterial vascular tone during the night in patients with essential hypertension.  J Hum Hypertens. 2007;  21 60-67
• 11 Middeke M.. Effect of nocturnal blood pressure measurement on sleep and blood pressure during sleep.  Z Kardiol. 1996;  85 (S 01) 99-105
• 12 Middeke M.. Drug effects on blood pressure rhythm in secondary hypertension.  Annals NY Academy of Science. 1996;  783 270-277
• 13 Middeke M.. Chronopathologie der Hypertonie: von der Praxishypertonie zur manifesten Hypertonie.  Fortschr Med. 1997;  115 57-58
• 14 Bock KD, Kreuzenbeck W.. Spontaneous blood-pressure variations in hypertension; the effect of antihypertensive therapy and correlations with the incidence of complications. In: Gross F, ed. Antihypertensive therapy-principles and practice.. Berlin-Heidelberg-New York: Springer; 1966: 224-237
• 15 Burnier M, Coltamai L, Maillard M, Bochud M.. Renal sodium handling and nightime blood pressure.  Semin Nephrol. 2007;  27 565-571
• 16 Davidson MB, Hix JK, Vidt DG, Brotman DJ.. Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate.  Arch Intern Med. 2006;  166 846-852
• 17 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
• 18 Farmer CK, Goldsmith DJ, Quin JD et al.. Progerssion of diabetic nephropathy – is diurnal blood pressure rhythm as important as absolute blood pressure level?.  Nephrol Dial Transplant. 1998;  13 635-639
• 19 Kempe HP, Hasslacher C.. Circadian variation of blood pressure in normo- and hypertensive diabetic patients with and without nephropathy.  Z Kardiol. 1996;  85 (S 03) 118-120
• 20 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
• 21 Palmas W, Pickering Th, 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
• 22 Sturrock ND, George E, Pound N et al.. Non-dipping circadian blood pressare and renal impairment are associated with increased mortalità in diabetes mellitus.  Diabet Med. 2000;  17 360-364
• 23 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
• 24 Boggia J, Thijs L, Hansen TW et al.. International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes (IDACO) investigators. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study.  Lancet. 2007;  370 1219-1229
• 25 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
• 26 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
• 27 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
• 28 Kario K, Pickering TG, Matsuo T et al.. Stroke prognosis and abnormal nocturnal blood pressure fall in older hypertensives.  Hypertension. 2001;  38 852-857
• 29 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
• 30 Muller JE, Stone PH, Turi ZG et al.. Circadian variation in the frequency of onset of acute myocardial infarction.  N Engl J Med. 1985;  313 1315-1322
• 31 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
• 32 Pierdomenico SD, 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
• 33 Verdecchia P, Porcellati C, Schillaci G et al.. Ambulatory blood pressure – an independent predictor of prognosis in essential hypertension.  Hypertension. 1994;  24 793-801
• 34 Reil JC Hrsg.. Archiv für die Physiologie.. Halle: Curt; 1796
• 35 Lemmer B.. The cardiovascular system and daily variation in response to antihypertensive and antianginal drugs: recent advances.  Pharmacol Ther. 1991;  51
• 36 Lemmer B.. Timing of cardiovascular medications-pitfalls and challenges.  Brit J Cardiol. 1995;  2 303-309
• 37 Lemmer B.. Chronopharmacokinetics: Implications for Drug Treatment.  J Pharm Pharmacol. 1999;  51 887-890
• 38 Lemmer B.. The importance of circadian rhythms on drug response in hypertension and coronary heart disease – from mice and man.  Pharmcol & Therapeutics. 2006;  111 629-651
• 39 Middeke M, Klüglich M, Holzgreve H.. Chronopharmacology of captopril plus hydrochlorothiazide in hypertension: morning versus evening dosing.  Chronobiology International. 1991;  8 506-510
• 40 Middeke M, von Bielinski C.. Antihypertensive chronotherapy in diabetes.  J Hypertens. 2008;  26 (S 01)
• 41 Portaluppi F, Vergnani L, Manfredini R et al.. Time-dependent effect of isradipine on the nocturnal hypertension of chronic renal failure.  Am J Hypertens. 1995;  8 719-726
• 42 Middeke M, Klüglich M.. Gestörte nächtliche Blutdruckregulation bei Hypertonikern im höheren Lebensalter.  Geriat Forsch. 1995;  5 125-132
• 43 Middeke M.. Die U-förmige Beziehung zwischen nächtlichem Blutdruck und Organschäden.  Dtsch Med Wochenschr. 2005;  130 2640-2642

Korrespondenz