Cardiac Function Improvement In

Hypertension Treated Patients

Ario Soeryo Kuncoro MD,Cardiologist

• Echocardiography Division
• Department Cardiology and Vascular Medicine, University of Indonesia
• National Cardiovascular Centre Harapan Kita, Jakarta
 Outline
• Hypertension burden in society

• Cardiac remodeling in hypertension

• Importance of antihypertensive medicine for

remodeling

• class specific effect for remodeling

• Summary/conclusion
Prevalence of HTN in Indonesia

Basic Health Research 2007

Recruited 19114 across 438 district
Uncontrolled hypertension carries the same
CV risk as untreated hypertension

Third National Health and Nutrition Examination Survey (NHANES III)

48%
Not treated (n = 2,458) Both are at equally
increased risk compared
with controlled BP
(p>0.05)
35%
BP
(n = 1,756)
uncontrolled

17%
BP controlled (n = 872)

Gu Q, et al. Am J Hypertens 2010;23(1):38-45

The Observed Relationship Between BP &
Vascular Disease Mortality
Meta-analysis of 61 prospective, observational studies for one million adults :

7% reduction in
risk of ischaemic
heart disease and
other vascular
2 mmHg disease mortality
decrease in
mean SBP

10% reduction in risk

Small SBP reductions of stroke mortality
yield significant
benefit

Lewington S, et al. Lancet. 2002;360:1903–1913.

 Ventricle Ischemia arrhythmia

Left ventricle microvascular

paroxysmal
hypertrophy angina/sichemia

macrovascular
diastolic dysfunction permanent
angina/ischemia

systolic dysfunction myocardial infarction embolic

 Incidence of CV events :
subdivided by tertile of LV mass index
Incidence of sudden death in LVH patient : Framingham Heart study

Haider. JACC.1998;5
•It is recommended that all patient with LVH
received antihypertensive agents (Class I)

•In patients with LVH, initiation of treatment with

one of the agents that have shown a greater
ability to regress LVH should be considered, i.e
ACE inhibitor, ARB and calcium antagonist
( Class IIa)

ESC/ESH Guideline for arterial hypertension management 2013

Changes in LV mass index with antihypertension therapy:
Meta analysis

Hypertens Res.2005;28:3
 Effect on Left Ventricular Hypertrophy

!  To evaluate the effect of Lercanidipine on the

regression of left ventricular hypertrophy (LVH)

!  hypertensive diabetics patients (54 patients) / non-

albuminuric NIDDM
!  52 weeks active treatment

!  Patients randomized to Lercanidipine 10 mg/d or

losartan 50 mg/d. Doses doubled after 8 weeks in non-
responders, then HCTZ 12.5 mg

!  Echocardiographic evaluation performed at the end of

the placebo period and after 12 months

Fogari R. et al. J Heart Disease 2001; 2: 38

 Left Ventricular Hypertrophy Reduction

BP change LVM change

0 0

-5
-5

-10
mmHg

g/sqm
-10
-15
95% CL:
p< 0.037
-15
-20
DBP
-25 SBP -20

Losartan 50 mg Lercanidipine 10 mg

Lercanidipine demonstrated a greater ability (P<0.037) than losartan to reduce LVH

Fogari R. et al. J Heart Disease 2001; 2: 38

Lercanidipine on Left Ventricular Hypertrophy
(LVH) reduction
Impact on
diastolic function

•Reduction of LVM related to

smaller LA diameter, shortened IVRT,Increase E/.A ratio,
prolonged DTime (vs no LVM regression , p<0,01)
•Diastolic parameter changes not associated with improve CV
mortality and morbidity
Circulation 2002;105:1071-76
Am J Cardiol 2010;106:999-1005
 CAP and surrogate
endpoints
• Longitudinal study

• Regression of LV mass was more strongly related to

change in CAP rather than Brachial arterial
pressure. After adjustment, only CAP remained
predictive

De Luca N,et al. REASON study group. J Hypertens 2004;22:1623-30

Central aortic pressure and mortality

Safar ME, et al. Hypertension 2002;39:735-38

HYPERTENSION IMPACT TO LARGE ARTERY

INFLAMMATION

INCREASE ARTERIAL STIFFNESS IN ESSENTIAL HYPERTENSION

PRIMARILY DUE TO INCREASE OF DISTENDING PRESSURE
HYPERTENSION 2005;45:1050
Lercanidipine on central blood pressure and
arterial stiffness in ISH

•  59#pts#>60#yrs#with#untreated#ISH#were#randomly#
assigned#to#receive#1#of#4#an@hypertensive#agents:#
perindopril,#atenolol,#lercanidipine,#or#bendrofluazide#

•  Peripheral#SBP#and#peripheral#PP#were#reduced#
similarly#aHer#treatment#with#all#4#classes#of#drug.##

•  However,#central#PP#was#only#reduced#significantly#by#
perindopril,#lercanidipine,#and#bendrofluazide,#whereas#
atenolol#had#no#effect#

•  Lercanidipine#reduced#the#augmenta@on#index,#
whereas#atenolol#increased#it#
Mackenzie,#Hypertension.#2009#Aug;54(2):409U13#
 Lercanidipine vascular protection
Effect on LVM and VESSELS

Objective / End point:

! Compare the effect of lercanidipine vs HCTZ on hypertension-related
cardiac and vascular structural alterations:
- forearm vascular resistence (FVR)
- calf vascular resistence (CVR)
- left ventricular mass index (LVMI)

Population:
! 24 mild-moderate hypertensive patients (mean age 47 yrs)

Design:
! Double-blind, randomized, parallel groups
! 52 weeks active treatment
! Patients randomized to LERCA 10 mg od or HCTZ 25 mg od
! parameters measured after 6 and 12 months of treatment

G. Serravalle et al. Am J Hypertens 2002;15: 39 A

 Lercanidipine vascular protection
reduction of vascular resistances

MAP (mmHg) LVMI FVR CRV

-9 0
-5
-10 -4,3
-10 -7,8
-9,5 -9,1
After 6 mos -11
-10,8 -15
of treatment
-12 -20
-21,1
-25
-13
-12,9 -30 Lercanidipine
-29,4
-14 -35 HCTZ

LVMI superimposable
After 12 mos
of treatment FVR and CRV >50% greater in the Lercanidipine
treated group

G. Serravalle et al. Am J Hypertens 2002;15: 39 A

 Lercanidipine Vessels protection
vascular flow & resistances

Grassi G. et al. 5th Scientific Meeting of AS of Hypertension 2000

 Impact of LV mass regression

regression

systolic function unchanged(improved at the midway

diastolic filling and relaxation uchanged or improved

abnormalities
autonomic nervous system changes toward normalization
dysfunction
ventricular arrhythmias reduced numbers

coronary reserve improved

associated vascular changes improved

SMALL ARTERY REMODELING

CURR HYPERTENS REP 2000;4:49

PHYSIOL REV 1990;70:921
BP and HR changes in patients treated different
doses of Lercanidipine in mild – moderate HBP

n.s.

p<0.001

p<0.001

Circo A. J Cardiovasc Pharmacol, 1997

 Lercanidipine in Asian patients
SBP and DBP values after 4 and 8 weeks of treatment

Lercanidipine#10420#mg#o.d.#
BP#(mmHg)#

Chia Y.C. et al. Singapore Med 2009; 50 (5): 500-505

 Lercanidipine in Asian patients:
SBP and DBP values after 4 and 8 weeks of treatment

Lercanidipine#10720#mg#o.d.#
BP#reduc)on#(mmHg)#

p < 0.0001

p < 0.0001

Chia Y.C. et al. Singapore Med 2009; 50 (5): 500-505

 summary
• Untreated Hypertension suffer from impact of
Cardiovascular system remodeling

• Antihypertensive management aim to reverse the

process and provide vascular protection

• Lercanidipine is vasoselective Ca Channel Blocker

which have role to reverse Cardiovascular remodeling
and protection

• Lercanidipine is able to provide BP control as

suggested by recent guidelines
Thank you