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Renin angiotensin system – old scripts, new movies
giotensinogen [AGT] gene, and A1166C polymorphisms of the angiotensin II type
I receptor gene [AGT1R]) were collected. Patients were assigned to 2 groups
(ACE inhibitor or No-ACE inhibitor) and followed for up to 12 years. Kaplan-Meier
curves and Cox regression models were used to demonstrate the survival and
major cardiovascular events (MACE) event-free survival trend. Pharmacogenetic
effects were determined by several Cox regression models.
Results: Of the 518 patients, 290 were treated with ACE inhibitors and 228 were
not. Prescription of ACE inhibitors was associated with a lower rate of MACE
at 4000 days. In addition, ACE I/D gene D was associated with a higher rate
of MACE in a multivariate regression analysis (HR: 1.64, 95% CI: 1.27∼1.98, P
< 0.001. This effect could be attenuated by the pharmacogenetic interaction of
ACE inhibitors and the ACE gene (ACE inhibitors*ACE D gene, HR: 0.68, 95%
CI: 0.52∼0.84, P = 0.014).
Cox regression models for MACE
Model 1
ACE D allele
ACE inhibitor
Model 2
ACE D allele
ACE inhibitor
D allele* ACE inhibitor
Hazard ratio
95% Confidence interval
P-value
1.52
0.51
1.34–1.97
0.41–0.86
0.003
0.032
1.44
0.62
0.68
1.21–1.85
0.51–0.94
0.52–0.84
0.004
0.009
0.014
All models adjusted for age, gender, diabetes, hypertension, and body mass index. ACE,
angiotensin-converting enzyme; AGT1R, angiotensin II type 1 receptor.
Conclusion: The use of ACE inhibitors was associated with a significant decrease in MACE in hypertensive patients diagnosed with CAD. Genetic variants
were also associated with event-free survival, but their effects were modified by
the use of ACE inhibitors.
J.Y. Park 1 , S.W. Rha 2 , J.W. Choi 1 , B.G. Choi 2 , S.Y. Choi 2 , C.U. Choi 2 , E.J. Kim 2 ,
C.G. Park 2 , H.S. Seo 2 , D.J. Oh 2 . 1 Eulji University, Seoul Eulji Hospital, Seoul,
Korea, Republic of; 2 Korea University Guro Hospital, Seoul, Korea, Republic of
Background: Angiotensin II has been shown to increase hepatic glucose production and decrease insulin sensitivity. Angiotensin converting enzyme inhibitor
(ACEI) or angiotensin receptor blocker (ARB) which are being extensively used
to control hypertension, are associated with a decreased incidence of new-onset
diabetes mellitus (DM). But, there have been limited data of different impact of
ACEI versus ARB on new-onset DM in Asian population.
Methods: We investigated total 1,856 patients (pts) who did not have DM from
January 2004 to September 2009. To adjust potential confounders, a propensity score matched (PSM) analysis was performed using the logistic regression
model. The primary end-point was the cumulative incidence of new-onset DM
which was defined as having a fasting blood glucose ≥126 mg/dL or HbA1c ≥
6.5%. Also, multivariable cox-regression analysis by aforementioned variables
was performed to determine the different impact of ACEI versus ARB on newonset DM.
Results: Mean follow-up duration was 963±293 days in all-pt group, and
970±288 days in PSM group. After PSM (C-statistics: 0.728), a total 642 baseline
adjusted pts (ACEI group=321 and control group = 321) were sorted out for analysis. In Kaplan-Meyer curve following both multivariate analysis and PSM, there
was no difference in the cumulative incidences of new-onset DM between ACEI
and ARB groups (p=0.145, figure).
Conclusions; In the present study, there was no difference in the cumulative incidences of new-onset DM between ACEI and ARB groups in a series of cardiovascular pts in Asian population.
G. Derosa 1 , A.F.G. Cicero 2 , A. D’Angelo 1 , A. Bonaventura 1 , L. Bianchi 1 ,
D. Romano 1 , P. Maffioli 1 . 1 University of Pavia, Pavia, Italy; 2 University of
Bologna, Bologna, Italy
Purpose: To evaluate the effects of a fixed olmesartan/amlodipine combination
on blood pressure control, lipid profile, and some insulin resistance parameters
compared to single monotherapies.
Methods: After a 2 week wash-out period, 276 hypertensive patients were randomly assigned to olmesartan 20 mg, amlodipine 10 mg or to a single pill containing a fixed dose of olmesartan/amlodipine 20/5 mg for 12 months. We evaluated
at baseline, after 6, and 12 months: body weight, body mass index (BMI), systolic
and diastolic blood pressure (SBP and DBP, respectively), fasting plasma glucose (FPG), fasting plasma insulin (FPI), HOMA index, lipid profile, adiponectin
(ADN), resistin (r), retinol binding protein-4 (RBP-4), vaspin, visfatin, omentin,
and chemerin. Furthermore, at the baseline, and after 6 and 12 months, patients
underwent an euglycemic, hyperinsulinemic clamp to assess M value.
Results: SBP and DPB were better decreased by olmesartan/amlodipine combination compared to amlodipine and olmesartan monotherapies (p< 0.01 for
both). No variations of lipid profile were recorded in neither of the three groups.
There was a decrease of FGP with olmesartan/amlodipine combination after 12
months compared to amlodipine monotherapy (p< 0.05). Olmesartan/amlodipine
combination decreased FPI and HOMA index both compared to baseline (p<
0.05), and compared to olmesartan and amlodipine monotherapies (p< 0.05 for
both), that did not alter these parameters. The olmesartan/amlodipine combination gave an increase of M value after 12 months, both compared to baseline (p<
0.01), to olmesartan monotherapy (p< 0.05), and to amlodipine monotherapy (p<
0.01). Both olmesartan, and olmesartan/amlodipine increased ADN and reduced
r (p< 0.01 vs baseline, for both), without significant differences between the two
groups. Olmesartan/amlodipine gave a decrease of both visfatin and vaspin after
12 months (p< 0.05, and p< 0.01 respectively), even if no differences in group
to group comparison were observed. None of treatments influenced RBP-4 levels. Finally, olmesartan/amlodipine significantly decreased chemerin and omentin
compared to single therapies (p< 0.05 for both).
Conclusions: Other than to be more effective in reducing blood pressure, olmesartan/amlodipine single pill combination gave also a major increase of insulin
sensitivity and a decrease of insulin resistance parameters compared to single
monotherapies.
1833 | BEDSIDE
Low salt intake and changes in serum sodium levels in the
combination therapy of low-dose hydrochlorothiazide and
angiotensin II receptor blocker
M. Nakayama 1 , H. Tomiyama 1 , I. Kuwajima 1 , A. Yamashina 1 , Y. Aizawa 2 . 1 Tokyo
Medical University, Tokyo, Japan; 2 Tachikawa general hospital, Cardiovascular
Center, nagaoka, Japan
Background: Although a low salt intake and angiotensin II blockade may act to
reduce serum sodium (srNa) levels during low-dose diuretic treatment, the effects
of these factors on srNa level have not yet been fully clarified. The present study
was conducted to examine the association of dietary salt intake with the changes
in srNa levels when angiotensin II receptor blocker (ARB) treatment is changed
to the combination of ARB plus a low-dose diuretic, Hydrochlorothiazide (HCTZ).
Methods: In 88 patients (age 70±12 years old), ARB treatment was switched
to the combination drug (the same dosage ARB plus 12.5 mg/day HCTZ). srNa
level was measured before and 6 months after administration of this combination
drug. The daily salt intake was estimated by the Kawasaki formula using second
morning urine.
Results: The study subjects were divided into quintile ranges according to the
daily salt intake. The reduction in srNa levels by switching to the ARB plus HCTZ
treatment was significant in subjects in the lowest quintile Q5 (7.22 g/day or less
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1831 | BEDSIDE
Angiotensin converting enzyme inhibitor versus angiotensin
receptor blocker on the incidence of new-onset diabetes mellitus
in Asian population
1832 | BEDSIDE
Effects of an olmesartan/amlodipine combination compared to
olmesartan or amlodipine monotherapies on some insulin
resistance parameters in hypertensive patients