e20 Abstracts / Journal of the American Society of Hypertension 9(4S) (2015) e19–e27
The resistant hypertension (RHTN) is defined by blood pressure
(BP)
140 / 90mmHg, despite the use of 3 or more antihypertensive agents
of different classes, including if possible a diuretic. Some hypertensive
patients are falsely categorized as RHTN due to non-adherence to pharma-
cological therapy. Therefore, it is essential the evaluation of adherence
with a reliable method in this group of patients. However, an ideal method
for this purpose is unknown. The triamterene emerges as a potential
biochemical marker of pharmacological adherence. The objective of this
work is the assessment of the adherence to pharmacological treatment
by direct method in RHTN subjects. A pilot test was conducted with
nine volunteers: six normotensives and three mild to moderate hyperten-
sives. A serial collection of urine was performed before and after admin-
istration of triamterene, until the 12-hour period. The ROC curve was
used to determine the fluorescence cutoff value of triamterene in the urine.
In addition, the evaluation of adherence in the RHTN patients (n ¼ 21) was
performed in three home visits by collecting urine. The adherent patients
should have the minimum fluorescence detected in all 3 visits. The patients
that administered triamterene showed a significant increase in the fluores-
cence values throughout the study period, as opposed to those who did not
take the medication. A fluorescence peak was observed up to 6 hours, and
therefore, this time was considered the ideal for analysis. In ROC curve
analysis, patients were considered adherents when the fluorescence was
above 0.44 x105. Among the 21 RHTN subjects evaluated, 9 patients
were considered adherents and 12 non-adherents. The fluorescence anal-
ysis of triamterene in urine may be considered a potential method of eval-
uation of drug adherence in patients with resistant hypertension.
Keywords: Resistant Hypertension; Medication adherence; Triamterene
P-5
Chronotherapy in hypertension: a pill at night makes things right?
Maria Leonarda De Rosa, Dario Leosco, Pasquale Abete, Nicola Ferrara.
University of Naples Federico II, Naples, Italy
Awareness and response to ticking biological clocks must be kept in mind
when constructing pertinent therapies, as evidence now supports the thesis
that knowledge of chronobiology is a concern when building a chrono-
therapy for hypertension .
Blood pressure(BP) displays appreciable predictable-in-time circadian
variation. The chronotherapy of hypertension takes into account the clini-
cally relevant features of the 24-h pattern of BP, e.g. the accelerated morn-
ing rise and nighttime decline during sleep, plus potential administration
circadian time determinants of the pharmacokinetics and dynamics of anti-
hypertensive medications .
Refractory arterial hypertension (RAH) is frequently associated to a non-
dipping BP pattern; this profile has been shown to have a worse clinical
prognosis. It is a common clinical practice that patients (p) receive anti-
hypertensive medication preferentially in the morning. Non-dipping could
be related to the timing of anti-hypertensive drug administration. We
analyzed whether switching anti-hypertensive medication to bedtime could
improve BP control in non-dipper p with RAH.
58 consecutive p with RAH and non-dipper or riser BP pattern on ambu-
latory BP (ABP) monitoring were studied before and after 6 weeks of a
change in the timing of anti-hypertensive medications. The intervention
consisted of shifting all non-diuretic anti-hypertensive drugs from morning
to evening, maintaining the same drugs at the same doses. A parallel group
of 28 consecutive p with similar characteristics and no changes in the ther-
apeutic regimen formed the control group.
There were 57% women, mean age 65.7  8.4 years. They were treated
with 4  0.7 anti-hypertensive drugs, 88% administered in the morning.
At baseline, diurnal and nocturnal ABP averaged 142.4  11.2/82.4 
10.1 and 143.4  12/79  7.9, respectively. After the drug shift, mean
diurnal and nocturnal ABP was 141.3  9.8/81.0  8.9 and 134.9 
11.9/71.9  10 (P ¼ 0.005 and 0.04 for systolic and diastolic ABP),
17% of the p restored a normal ABP circadian rhythm. No changes
were observed in the control group.
In non-dipper or riser p with RAH, changing the timing of anti-
hypertensive medication to the evening could improve BP control.
Nocturnal hypertension, which is characterized by the loss or even reversal
of the expected 10-20% sleep-time BP decline, increases the risk of cardiac
and cerebrovascular events. Chronotherapy provides a means of individu-
alizing treatment of hypertension according to the circadian profile of BP
of each patient. The chronotherapeutic strategy constitutes a new option to
optimize BP control and to reduce risk.
Keywords: Chronotherapy; Refractory arterial hypertension; Circadian
profile
P-6
Barnidipine compared to lercanidipine in addition to losartan on
endothelial damage and oxidative stress parameters in patients with
hypertension and type 2 diabetes mellitus
Giuseppe Derosa,4 Fabrizio Querci,1 Ivano Franzetti,2 Pietrp Ragonesi,3
Angela D’Angelo,4 Pamela Maffioli.4 1Ospedale Pesenti Fenaroli, Alzano
Lombardo, Italy; 2S. Antonio Abate Hospital, Gallarate, Italy; 3S. Carlo
Hospital, Milano, Italy; 4University of Pavia, Pavia, Italy
Aim: To evaluate the effects of barnidipine or lercanidipine, in addition to
losartan, on some markers linked to endothelial damage and oxidative
stress in patients with hypertension and type 2 diabetes mellitus.
Methods: We enrolled 151 hypertensive patients with mild to moderate
hypertension [systolic blood pressure (SBP)
140 and <180 mmHg
and diastolic blood pressure (DBP)
90 and <105 mmHg], type 2 dia-
betes mellitus, normocholesterolemic (low density lipoprotein cholesterol
<160 mg/dl). Patients were randomised to barnidipine, 20 mg/day, or ler-
canidipine, 20 mg/day, both in addition to losartan, 100 mg/day, for 6
months. We assessed BP monthly, in addition, patients underwent ambula-
tory blood pressure monitoring (ABPM) at baseline, and at the end of the
study. We also collected blood sample to assess: fasting plasma glucose
(FPG), glycated hemoglobin (HbA1c), some adipocytokines linked to
endothelial damage such as high-sensitivity C-reactive protein (Hs-CRP),
tumor necrosis factor-a (TNF-a), metalloproteinase-2 (MMP-2) and -9
(MMP-9), soluble vascular adhesion protein-1 (sVCAM-1), soluble inter-
cellular adhesion protein-1 (sICAM-1). We also evaluated some markers
of oxidative stress such as isoprostanes and paraoxonase-1 (PON-1).
Results: One hundred and forty-three patients completed the study. Both
barnidipine and lercanidipine resulted in a significant reduction in SBP
and DBP (p < 0.001 vs baseline for barnidipine + losartan and p < 0.01
for lercanidipine + losartan), even if the blood pressure reduction obtained
with barnidipine + losartan was greater than that obtained with lercanidi-
pine + losartan (p < 0.05). Data recorded with ABPM also showed a
similar trend. Barnidipine + losartan reduced the levels of Hs-CRP and
TNF-a (p < 0.05 vs baseline and vs lercanidipine + losartan). There
were no significant differences between the two treatments on the levels
of MMP-2 and -9. Barnidipine + losartan significantly reduced the levels
of sVCAM-1 and sICAM-1 after 6 months of treatment, both compared
to baseline and to lercanidipine + losartan (p < 0.05 for both). The levels
of isoprostanes were reduced by barnidipine + losartan (p < 0.05 vs base-
line and vs lercanidipine + losartan), while the levels of PON-1 remained
unchanged with both treatments.
Conclusions: Other than giving a greater reduction of blood pressure, bar-
nidipine + losartan gave an improvement of some parameters linked to
endothelial damage and oxidative stress in diabetic and hypertensive
patients.
Keywords: Barnidipine; Lercanidipine; Endothelial damage
P-7
Antihypertensive drug therapy and prevention of coronary heart
disease events in clinical trials
Mercades Diaz, William J. Elliott. Pacific Northwest University of Health
Sciences, Yakima, WA, United States