Nocturnal Hypertension: Neglected Issue in Comprehensive Hypertension Management

.........., Rensa/Yudis2
1. Faculty of Medicine, Atmajaya Catholic University of Indonesia, Jakarta, Indonesia.
2. Department of Internal Medicine, Faculty of Medicine, Atmajaya Catholic University of
Indonesia, Jakarta, Indonesia.
Correspondence author:
Faculty of Medicine, Atmajaya Catholic University of Indonesia, Jakarta, Indonesia.
Email:
Introduction
Hypertension had been long time well studied as one of main cardiovascular disease (CVD)
risk factor, that made every physicians routinely prescribed anti hypertensive drug to
maintain normal blood pressure.1 However, the diagnosis of nocturnal hypertension tend to be
missed although it was important predictor of all cause mortality and/or cardiovascular
mortality.2 Lack of awareness with hypertension made the patients measure their blood
pressure only in hospital visit. This factor contributed to the limited use of ambulatory blood
pressure measurement, and the possibility of nocturnal hypertension became overlooked.3 In
this review, we described the definition, epidemiology, pathophysiology, clinical significance,
diagnosis, and anti hypertension management of isolated hypertension.

Pathophysiology of Nocturnal Hypertension

Many factors were postulated can disrupt the circadian rhythm, which in turn lead to
attenuation of nocturnal blood pressure lowering phenomenon. The causes of abnormal
circadian rhythm of blood pressure can be divided to hormonal metabolic factors and external
factors such as smoking or aging. Some disease are implicated in the disruption, such as
diabetes mellitus, metabolic syndrome, chronic kidney disease, and obstructive sleep apnea
(OSA).4 In this paper, we described the two most reported mechanism of nocturnal
hypertension, which were imbalance of nocturnal autonomic nervous system and limited
sodium metabolism by kidneys.
Imbalance of nocturnal autonomic nervous system activation
Normally, blood pressure level is fluctuated along the day with peak rise in early morning and
low while sleeping. Circadian rhythm is one of the contributor of the fluctuation which
controlled from suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Circadian
rhythm mainly influenced by autonomic nervous system.a In general, Autonomic nervous
system composed of sympathetic and parasympathetic nerves, which keep in balance to
maintain physiologic state. Over dominant of sympathetic activation were postulated as the
cause of nocturnal hypertension and attenuated the blood pressure dipping. Vardhan et al
reported that, patients with obstructive sleep apnea (OSA) were having higher catecholamines
plasma and urinary level compared with control. This findings were correlated with
hypertension in patient with OSA.b Nielsen et al, found that low degree of blood pressure
dipping were related to sustained adrenergic activity which reflected by higher noradrenaline
level and lead to decreased the peripheral vasodilatation capacity.c Doxazosin, an alpha-1
adregenic, will effectively block the sympatethic activity which in turn lower the blood
pressure while sleeping.d
Limited sodium metabolism
Kidneys are having role for maintaining blood pressure, regulated by renin-angiotensinaldosteron system and influenced by circadian rhythm. Non dipping patient are thought to be
related with impaired capacity of kidneys to excrete sodium during daytime or Increased
tubular sodium reabsorption which was commonly caused by hyperaldosteronisme,f This
theory was supported by data that the prevalence of nondipper increased in patient with low

glomerular filtration rate (GFR).g Farmar et al, found there was direct correlation between
plasma creatinine level and percent of blood pressure declining at night. From their 380
patients retrospective data, non-dipping phenomenon were more prevalent in CKD patients
(53%) than in patients with essential hypertension (30%).h Wang et al reported among 540
Chinese CKD patients, total of 21,9% patients had nighttime blood pressure increased
(reversed dipper), 36,1 % patients were dipper, and 42% of patients were non-dipper.i
However, increased daily salt intake also found to be related with nocturnal hypertension
Kidneys will compensate high sodium intake by enhancing natriuresis during the night,
resulting in elevated nighttime blood pressure. Blood pressure will remain elevated until
kidneys succeed in reducing excess sodium.k

1. Padwal R, Straus SE, McAlister FA. Cardiovascular risk factors and their effects on the
decision to treat hypertension: evidence based review. BMJ. 2001 Apr 21;322(7292):97780.
2. Friedman O, Logan AG. Can nocturnal hypertension predict cardiovascular risk? Integr
Blood Press Control. 2009 Sep 4;2:2537.
3. Li Y, Wang J-G. Isolated Nocturnal Hypertension A Disease Masked in the Dark.
Hypertension. 2013 Feb 1;61(2):27883.

4. Kanbay M, Turgut F, Uyar ME, Akcay A, Covic A. Causes and mechanisms of nondipping
hypertension. Clin Exp Hypertens. 2008 Oct;30(7):58597.

a. Biaggioni I. Circadian Clocks, Autonomic Rhythms, and Blood Pressure Dipping.

Hypertension. 2008 Nov 1;52(5):7978.
b. Vardhan V, Shanmuganandan K. Hypertension and catecholamine levels in sleep apnoea.
Med J Armed Forces India. 2012 Jan;68(1):338.
c. Nielsen FS, Hansen HP, Jacobsen P, Rossing P, Smidt UM, Christensen NJ, et al. Increased
sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with
diabetic nephropathy. Diabet Med. 1999 Jul;16(7):55562.

d. Yasuda G, Hasegawa K, Kuji T, Ogawa N, Shimura G, Umemura S, et al. Effects of

doxazosin on ambulatory blood pressure and sympathetic nervous activity in hypertensive
Type 2 diabetic patients with overt nephropathy. Diabet Med. 2005 Oct;22(10):1394400.
e. Bankir L, Bochud M, Maillard M, Bovet P, Gabriel A, Burnier M. Nighttime Blood Pressure
and Nocturnal Dipping Are Associated With Daytime Urinary Sodium Excretion in African
Subjects. Hypertension. 2008 Apr 1;51(4):8918.
f. Zelinka T, trauch B, Pecen L, Widimsk J. Diurnal blood pressure variationin
pheochromocytoma, primary aldosteronism and Cushings syndrome. J Hum Hypertens.
2004;18(2):10711.
g. Isobe S, Ohashi N, Fujikura T, Tsuji T, Sakao Y, Yasuda H, et al. Disturbed circadian rhythm
of the intrarenal renin-angiotensin system: relevant to nocturnal hypertension and renal
damage. Clin Exp Nephrol. 2014 Apr 12;19(2):2319.
h. h. Farmer CK, Goldsmith DJ, Cox J, Dallyn P, Kingswood JC, Sharpstone P. An investigation
of the effect of advancing uraemia, renal replacement therapy and renal transplantation on
blood pressure diurnal variability. Nephrol Dial Transplant. 1997 Nov 1;12(11):23017.
i. Wang C, Zhang J, Liu X, Li C, Ye Z, Peng H, et al. Reversed Dipper Blood-Pressure Pattern
Is Closely Related to Severe Renal and Cardiovascular Damage in Patients with Chronic
Kidney Disease. PLoS ONE. 2013 Feb 5;8(2):e55419.
j. Shin J, Xu E, Lim YH, Choi BY, Kim BK, Lee YG, et al. Relationship between nocturnal
blood pressure and 24-h urinary sodium excretion in a rural population in Korea. Clinical
Hypertension. 2014 Sep 25;20(1):9.
k. Kimura G, Dohi Y, Fukuda M. Salt sensitivity and circadian rhythm of blood pressure: the
keys to connect CKD with cardiovasucular events. Hypertens Res. 2010 Jun;33(6):51520.