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Deal with Non-dipping Status: Chronotherapy
The non-dipping pattern refers the situation of impaired circadian BP rhythm, and
it is defined as decrement in SDP and/or DBP less than 10% during the night. Non-
dipper has particular importance, and the prevalence of abnormally high sleep BP is
very often in CKD patients. It was shown that the capacity of excreting sodium dur-
ing daytime is a significant determinant of nocturnal BP and dipping pattern as
reduced capacity leads to higher nocturnal BP and non-dipping pattern [ 21 ]. Non-
dipping BP is associated with target organ damage including left ventricular hyper-
trophy, higher prevalence of proteinuria and higher risk of CKD progression, and
poorer cardiovascular outcomes. In patients with true resistant hypertension, non-
dipping pattern is associated with nearly twofold increased risk of cardiovascular
morbidity and mortality. Thus, therapeutic restoration of normal physiologic BP
reduction during nighttime sleep (dipping status) is the most significant indepen-
dent predictor of decreased risk and the basis for the chronotherapy. Chronotherapy
is a therapeutic strategy of taking at least one dose of antihypertensive medications
at bedtime, instead of all in the morning time to provide dipping status (normal
circadial variation) and ABMP control.
Chronotherapy Against to Non-dipping Pattern
Several studies have investigated the effect of chronotherapy on the ABPM control
and the non-dipping pattern. The Monitorización Ambulatoria para Predicción de
Eventos Cardiovasculares (MAPEC) is a prospective randomized study which
examines the effect of chronotherapy on ABPM and clinical outcomes (primary
endpoint including composite of all-cause mortality and cardiovascular events) in
2156 patients with untreated or resistant hypertension [ 22 ]. Study population
divided into two groups consisting of control group, took all antihypertensive medi-
cations in the morning and the treatment group and took one or more antihyperten-
sive at bedtime. Patients were followed during median of 5.6 years with a primary
composite endpoint of all-cause mortality and total cardiovascular events. 48-h
ABPM was performed to patients at least annually. Patients randomized to the treat-
ment arm (bedtime administration) demonstrated lower sleep-time BP, a higher rate
of controlled ABPM (62% vs. 53%, p < 0.001), and a much lower incidence of the
non-dipper status (34% versus 62%, p < 0.001). As a clinical outcome, those in the
bedtime administration group had a reduction in the primary endpoint of 11.95 ver-
sus 27.8 events per 1000 patient-years, NNT = 63 over 1 year. All-cause mortality
alone was also reduced (2.11 versus 4.16 events per 1000 patient-years, NNT 488
over 1 year). It has been concluded that switching at least one medication to bedtime
administration is cost-effective, simple intervention that contributes to improve BP
control and reduce cardiovascular events. In another interesting study, 27 consecu-
tive patients with resistant hypertension and non-dipper BP pattern on ABPM were
enrolled to investigate whether shifting all non-diuretic antihypertensive drugs from
M. Ya rl iog lu e s