Fibrillation and Hypertension Quo Vadis Osung Kwon MD Asan Medical Center Hopefully University of Minnesota Next Year Contents Introduction Epidemiology and What the problem is The ID: 497980
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Slide1Slide2
Atrial
Fibrillation and Hypertension, Quo Vadis ?
Osung
Kwon, MD.
Asan
Medical Center
Hopefully University of Minnesota Next YearSlide3
Contents
Introduction – Epidemiology and What the problem is
The
pathophysiogic
links between HTN and AF
The current major clinical issues
Dilemma regarding BP measurement in case of AF
Antihypertensive therapy - Reducing AF
Therapy for chronic AF - Gaining with BP lowering medication
Antithrombotic therapy in AF - Risk in hypertensive patients
Unanswered questions and future perspectives
ConclusionSlide4Slide5
Chugh
SS et al.
circluation
, 2014Slide6
Introduction
AF is the most common chronic arrhythmia associated with significant morbidity and mortality, and is a growing epidemic world-wide.
A growing burden of AF is inevitable due to aging population and the accompanying increase in the prevalence of cardiovascular risk factors such as hypertension.
Hypertension is the most common cardiovascular disorder, firmly recognized the primary risk factor for AF and the prevalence increases with age. Slide7
Despite
such a close link between the two conditions,
management
and prognostic implication
of hypertension, specifically
related to
AF,
have not been well recognized.
Herein we review the interplay between
hypertension
and AF with focus on the practical management of hypertension in patients with AF.Slide8
Pathophysiologic
association
How does increased BP lead to AF?
The
persistent elevation of
blood pressure
results in
LV hypertrophy
and
LV dysfunction, leading LA
enlargement and pulmonary veins dilation with a
high level of stretch.
The distention and stretching of these structures
provoke
atrial
fibrosis, a hallmark of
arrhythmogenic
structural changes, and initiate
electrophysiological alteration
vulnerable
to development of AF.
Atrial
structural and electrical remodeling are central to genesis of AF.Slide9
Atrial
structural remodeling
Structural remodeling is characterized by
atrial
enlargement and
tissue-fibrosis
Burstein B et al. JACC, 2008Slide10
Atrial
electrical remodeling
The principal components is decreased L-type Ca2
+
-current, increased inward-rectifier K
+
current and abnormal expression/distribution of the gap junction
connexin
hemichannels
.
AF begets AF
Iwasaki YK, circulation, 2011Slide11
Inflammation - HTN & AF
Activated
macrophages cause ROS generation and endothelial dysfunction that lead to vascular dysfunction and
remodeling results in
increasing blood pressure.
Endothelial dysfunction and oxidative stress
has been implicated as a mechanism that medicates the effects of inflammation in
AF.
Various inflammatory markers or modulators including CRP, TNF-
α
, IL-6 are associated with HTN and AF.
It is likely that inflammation may play a role in the initiation and maintenance of AF while AF seems to create and sustain an inflammatory.Slide12
Autonomic imbalance – HTN & AF
The mechanisms of increased sympathetic tone in
hypertenstives
involve
angiotensin
II
with excitatory
effects on sympathetic
outflow,
hyperinsulinemia
, excessive
hypothalamic drive,
impairment
of arterial
baroreflex
.
Adrenergic-dependent RyR2
phosphorylation
increases SR Ca2
+
leak and causes abnormal DAD-promoting Ca2
+
handling that elicits Ca2
+
sparks and triggers ectopic firing.
Vagal
activation is related to a spatially heterogeneous reduction in
atrial
ERP so that promotes the initiation and stabilization of multiple AF-maintaining reentrant rotors.Slide13
Hypertension
LV hypertrophy
LV dysfunction
Renin-anigotensin
aldosterone
system
LA enlargement with stretching
Sympathetic activation
(Autonomic imbalance)
Inflammation
Endothelial dysfunction
Oxidative stress
Atrial
fibrillation
Atrial
structural remodeling
Atrial
electrical remodeling
Altered
Ca
2+
handling
Iron channel changes
Atrial
fibrosisSlide14
The major clinical issues
Dilemma regarding BP measurement in case of AF
Antihypertensive therapy - Reducing AF
Therapy for chronic AF - Gaining with BP lowering medication
Antithrombotic therapy in AF - Risk in hypertensive patientsSlide15
How to measure accurate BP
in case of AF
There is no firmly recommended method for measuring BP in AF subjects.
Automated electronic devices are being popularly used in general. Accuracy
of
these devices in AF subjects is a
major and timely clinical issue
.
Available reports including recent meta-analysis suggest that the automated BP method is acceptable in measuring SBP but not DBP in AF subjects, may be proposed for out-of office measurement method but not for office.Slide16
Ambulatory blood pressure monitoring (ABPM) allows identification of white-coat and masked hypertension phenomena, detects nocturnal hypertension, is a stronger predictor of CV morbidity and mortality than office measurement
ABPM provided data with similar variability and repeatability in AF subjects as in subjects with normal rhythm, indicating ABPM is applicable in AF
.Slide17
Prevention of AF using antihypertensive treatment
Helst
EK et al.
Prog
Cardiovasc
Dis
, 2006Slide18
RAS inhibitors
Primary prevention
RAS inhibition has protective effects on AF, especially in subjects with LVH, LV dysfunction.
Secondary prevention
RAAS inhibitors may not prevent AF recurrence in subjects with paroxysmal AF or those receiving
cardioversion
.
RAAS inhibitors have additional protective effect beyond the BP control: decreasing of
atrial
stretch, lowering LVEDP and LA pressure, prevention of
atrial
fibrosis, modification of sympathetic tone,
atrial
refractoriness, and direct
antiarrhythmic
effects Slide19
β
-Blockers
Primary prevention
In
a systematic
review, beta-blockers reduced
incidence of onset of AF by
27% in CHF subjects.
Secondary prevention
A
randomized trial demonstrated
that
metoprolol
reduced modestly but significantly relapse of AF or AFL after
cardioversion
(
59.9%
vs
48.7%; P=0.005).
Mechanisms of action of β -blockers to reduce AF risk may be preventing adverse remodeling and ischemia, reducing sympathetic drive, or counteracting the β -adrenergic shortening of action potential.Slide20
CCBs, Diuretics and
Renal sympathetic
denervation
In terms of primary prevention of AF, CCBs have shown inferior to RAS inhibitors in reducing AF.
The
effect of diuretics on reducing the risk of AF has not been thoroughly investigated
. There has been reports that
thiazide
-induced
hypokalemia
contributes to development of AF.
Animal models and a few clinical reports showed the protective effects of renal
denervation
on AF recurrence in
hypertensives
. Several trials is ongoing to address the effects of renal
denervation
on AF Slide21
Benefits with BP lowering
medication for chronic AF
Chronic AF can lead to a number of serious clinical consequences. Thus, adequate BP control is considered one of important modifiable factors in risk reduction.
Patients with a mean systolic pressure of over 140 mmHg were associated with increased risk of stroke and systemic embolic events.
However, there is no trial to address whether and how BP lowering medications reduce the morbidities and mortality in AF subjects. Slide22
Risk in hypertensive patients with Antithrombotic therapy in AF
Uncontrolled
hypertension (usually defined as systolic BP > 160 mmHg or diastolic > 100 mmHg) is firmly associated with a higher bleeding
risk.
No
evidence
suggest
that treated hypertension increases the risk of
bleeding.
The new
anticoagulants also
have slightly lower
bleeding risks than
warfarin
, but
considerable. No
report
exists yet to
examine the
effects
of
BP control on bleeding complications
of
these new agents.Slide23Slide24
Unanswered questions and
Future perspectives
Subjects with AF are unique population in terms of BP?
The optimal BP management in subjects with AF
Who (ethical, gender differences? or
comorbidities
?)
Where (lower is better or “J”-curve?)
How (accurate BP measurement, optimal medications?)
The clinical benefits of new antihypertensive treatments (e.g. anti-inflammatory and anti-
symphathetic
) for AF subject with HTN.
The relationship between AF and aortic stiffness
The relationship between AF and
prehypertension
(e.g. non-dipper)Slide25
Conclusions
HTN is the most common attributed risk factor for the increasing burden of AF in aging population.
The
pathophysiologic
link between HTN and AF has been demonstrated. Further studies are warranted to clarify the mechanisms and its clinical implications.
For prevention and treatment of AF, optimal blood pressure management should be addressed.Slide26