Dr. Page is an associate professor of clinical pharmacy and physical medicine and a clinical specialist, Division of Cardiology, University of Colorado Health Sciences Center, Schools of Pharmacy and Medicine.
As with most biologic processes,
blood pressure (BP) demonstrates
a distinct circadian
rhythm, characterized by a substantial
reduction during sleep (the nocturnal
dip) followed by a moderate to marked
increase around the time of awakening
(the morning surge). It is not surprising
that the onset of acute cardiovascular (CV)
events (eg, myocardial infarction, sudden
cardiac death, and stroke) also shows
a circadian pattern, with peak occurrence
during the early morning hours.1,2
In patients with hypertension, this surge
in BP (eg, above 135/85 mm Hg) during
the first 2 hours after waking, but not in
the evening (the last 2 hours before going
to bed) has been defined as morning
hypertension.3 This morning BP surge has
pathological significance as it is positively
related to degree of target-organ damage,
such as carotid intima-media thickness
and left ventricular hypertrophy.4-6 The
magnitude of the morning surge also is an
independent predictor of cerebrovascular
and cardiac events.7
Nondippers Versus Extreme Dippers
Two types of morning hypertension exist.8-10
The patients who demonstrate a nocturnal
decrease in BP that is <10% of their
daytime BP are known as nondippers. The
other type of patients are the extreme dippers
who exhibit a 20% or more decrease
in nocturnal BP, compared with daytime
BP. Finally, a patient can be an inverted
dipper/riser in which their BP does not
decrease or actually may increase at night.
Nondippers and risers typically do not
show a surge in BP on awakening but usually
have sustained early morning hypertension.
An excessive morning surge is
common in extreme dippers.8-10
What Causes Morning Hypertension?
The morning surge in BP is influenced by
many pathophysiological factors, such as
activity of the autonomic and renin-angiotensin-
aldosterone systems and dietary
sodium intake. Other alterations that
occur during the early morning that can
have a significant impact on increasing CV
risk in this population include increased
heart rate, vascular tone, blood viscosity,
and platelet aggregability. With the advent
of ambulatory blood pressure monitoring
(ABPM), this technology has improved
identification of patients with excessive
morning surges and has facilitated assessment
of antihypertensive agents that may
be particularly effective in this subgroup
of the hypertensive population.11,12
In the Japan Morning Surge-1 study,
Ishikawa and colleagues used ABPM in
611 patients with morning hypertension
to determine important patient-specific
characteristics.13 The analysis showed
that patients with morning hypertension
are more likely to be of older age, as well
as have a longer duration of hypertension
and antihypertensive medication use, display
a higher prevalence of left ventricular
hypertrophy with an elevated B-type natriuretic
peptide concentration, and exhibit a
lower glomerular filtration rate.
As for pharmacotherapy, choice of an
agent is dependent upon the pharmacokinetics
and formulation of the drug,
published evidence, and timing of administration.
Medications with long half-lives,
such as telmisartan, amlodipine, chlorthalidone,
and bisoprolol, have demonstrated
efficacy in controlling early morning BP.
Bedtime administration of chronotherapeutic
preparations as well as alphablockers
such as doxazosin have also
been effective, particularly when used in
combination with ABPM.14-24
This communication on the importance of home blood pressure monitoring is supported by Omron Healthcare, Inc. It is intended to help pharmacists and their staff understand the importance of home blood pressure monitoring.
- Cohen MC, Rohtla KM, Lavery CE, Muller JE, Mittleman MA. Meta-analysis of the morning excess of acute myocardial infarction and sudden cardiac death. Am J Cardiol. 1997;79(11):1512-1516.
- Muller JE, Ludmer PL, Willich SN, et al. Circadian variation in the frequency of sudden cardiac death. Circulation. 1987;75(1):131-138.
- Pickering TG. Morning hypertension. J Clin Hypertens (Greenwich). 2007;9(3):224-228.
- Giles TD. Circadian rhythm of blood pressure and the relation to cardiovascular events. J Hypertens Suppl. 2006;24(2):S11-16.
- Pol?nia J, Amado P, Barbosa L, et al. Morning rise, morning surge and daytime variability of blood pressure and cardiovascular target organ damage. A cross-sectional study in 743 subjects. Rev Port Cardiol. 2005;24(1):65-78.
- Marfella R, Siniscalchi M, Nappo F, et al. Regression of carotid atherosclerosis by control of morning blood pressure peak in newly diagnosed hypertensive patients. Am J Hypertens. 2005;18(3):308-318.
- 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(8):581-587.
- Ohkubo T, Imai Y, Tsuji I, et al. Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study. Am J Hypertens. 1997;10(11):1201-1207.
- White WB. Clinical assessment of early morning blood pressure in patients with hypertension. Prev Cardiol. 2007;10(4):210-214.
- Kario K, Shimada K. Risers and extreme-dippers of nocturnal blood pressure in hypertension: antihypertensive strategy for nocturnal blood pressure. Clin Exp Hypertens. 2004;26(2):177-189.
- Sica DA. What are the influences of salt, potassium, the sympathetic nervous system, and the renin-angiotensin system on the circadian variation in blood pressure? Blood Press Monit. 1999;4(Suppl 2):S9-S16.
- Pickering TG, Miller NH, Ogedegbe G, et al. Call to action on use and reimbursement for home blood pressure monitoring: executive summary: a joint scientific statement from the American Heart Association, American Society Of Hypertension, and Preventive Cardiovascular Nurses Association. Hypertension. 2008;52(1):1-9.
- Ishikawa J, Hoshide S, Shibasaki S, et al. Relationship between morning hypertension identified by home blood pressure monitoring and brain natriuretic peptide and estimated glomerular filtration rate: the Japan Morning Surge 1 (JMS-1) Study. J Clin Hypertens (Greenwich). 2008;10(1):34-42.
- Mengden T, Battig B, Schubert M, et al. Comparison of casual, ambulatory and self-measured blood pressure in a study of nitrendipine vs bisoprolol. Eur J Clin Pharmacol. 1992;42(6):569-575.
- White WB, Sica DA, Calhoun D, Mansoor GA, Anders RJ. Preventing increases in early-morning blood pressure, heart rate, and the rate-pressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising. Am Heart J. 2002;144(4):657-665.
- Glasser SP, Neutel JM, Gana TJ, Albert KS. Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension. Am J Hypertens. 2003;16(1):51-58.
- Eguchi K, Kario K, Hoshide Y, et al. Comparison of valsartan and amlodipine on ambulatory and morning blood pressure in hypertensive patients. Am J Hypertens. 2004;17(2):112-117.
- White WB, Lacourciere Y, Davidai G. Effects of the angiotensin II receptor blockers telmisartan versus valsartan on the circadian variation of blood pressure: impact on the early morning period. Am J Hypertens. 2004;17(4):347-353.
- White WB, Lacourciere Y, Gana T, et al. Effects of graded-release diltiazem versus ramipril, dosed at bedtime, on early morning blood pressure, heart rate, and the rate-pressure product. Am Heart J. 2004;148(4):628-634.
- 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;27(4):369-376.
- Lacourciere Y, Neutel JM, Davidai G, Koval S. A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring. Am J Hypertens. 2006;19(1):104-112.
- Williams B, Gosse P, Lowe L, Harper R; PRISMA I Study Group. The prospective, randomized investigation of the safety and efficacy of telmisartan versus ramipril using ambulatory blood pressure monitoring (PRISMA I). J Hypertens. 2006;24(1):193-200.
- Gosse P, Neutel JM, Schumacher H, et al. The effect of telmisartan and ramipril on early morning blood pressure surge: a pooled analysis of two randomized clinical trials. Blood Press Monit. 2007;12(3):141-147.
- Wright JT, Jr, Harris-Haywood S, Pressel S, et al. Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2008;168(2):207-217.