1.

Understanding
Sympathetic
overdrive

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 What is sympathetic overdrive?

1 Sympathetic neural factors are involved in multiple

homeostatic functions including energy balance and
blood pressure control1

2 Chronic sympathetic activation

(or sympathetic overdrive) has been implicated in
the development of metabolic syndrome and other
cardiovascular risk factors1,2

3 Sympathetic overdrive is triggered by:

• Reflex mechanisms
(arterial baroreceptor impairment)
• Metabolic factors (insulin resistance)
• Humoral factors (angiotensin II, leptin)1

1. Grassi G. Sympathetic overdrive and cardiovascular risk in the metabolic syndrome. Hypertens Res. 2006;29:839–47.
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2. Egan BM, Basile J, Chilton RJ et al. Cardioprotection: the role of β-blocker therapy. J Clin Hypertens. 2005;7(7):409–16.
contents 3. License granted by alila© 123RF.com. Sympathetic pathway of the ANS (system, nervous, anatomy).
 Sympathetic overdrive is associated with increased heart rate and multiple
cardiovascular risk factors1,2

Sympathetic overactivity

 Hematocrit Increased heart rate

 Plasma volume
 O2 consumption,  Artery wall LV apoptosis
Arteriolar constriction
ventricular arrhythmias stress Collagen fibrosis
Venoconstriction

Endothelial
 Cardiac output  Muscle blood flow LV stiffness
dysfunction

Hypertension Insulin resistance Obesity Atherosclerotic LV systolic

plaque dysfunction

Lipid abnormalities Inflammation

Coronary events Heart failure

Graph adapted from references 1-2 Sudden death

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1. Adapted from Palatini P. Heart rate and the cardiometabolic risk. Curr Hypertens Rep. 2013;15:253–59
contents 2. Heusch G. Heart rate and heart failure: not a simple relationship. Circ J. 2011;75:229-36.
 Sympathetic overdrive plays a key role in the pathophysiology of
cardiovascular disease1

 Sympathetic nervous activity

Neural release of norepinephrine1

1 1
Beta1 receptor stimulation Beta1 receptor stimulation
Mechanical/
vascular damage
• Pulsatile stress on
vascular system1  Renin release1
 Heart rate1 • Augment atherosclerosis1  Angiotensin1
 Heart rate variability1 • Plaque rupture1  Blood pressure1
 Contractility1 • Risk of cardiac ischemia1  Left ventricular hypertrophy1
 Heart failure1

Graph according to reference 1

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1. Egan BM, Basile J, Chilton RJ et al. Cardioprotection: the role of β-blocker therapy. J Clin Hypertens. 2005;7(7):409–16.
contents
SO was found in prehypertension

This study measured HRR of 91 subjects with PHT, 44 patients with hypertension, and 53 normotensive healthy volunteers. HRR was significantly
lower in the HT and PHT groups as compared to the control group (24.4±5.7, 26.0±8.4, 30.0±8.7; hypertension, PHT, and control groups, respectively)

International Journal of Cardiology 151 (2011) 50–53 IDN/CONCO/0319/0012

SO contributes to the development of HT

Increased vascular tone

Increased
Altering renal sodium and water
sympathetic hypertension
homeostasis
activity

Inducing cardiac and vascular

remodeling

International Journal of Cardiology 151 (2011) 50–53 IDN/CONCO/0319/0012

 Sympathetic overdrive leads to multiple responses that contribute to heart
failure and sudden death1

Sympathetic nervous system activation

 RAAS  Myocardial  Myocyte  Coronary  Electrolyte Progressive Cytokine

 HR
activation reserve contractility blood flow abnormalities cardiac remodeling activation

Heart rate (HR) Renin angiotensin aldosterone system (RAAS)

 Response  Arrhythmia Cardiac

Vasoconstriction Ischemia
to exercise risk dysfunction

Heart failure Sudden death

Graph adapted from reference 1

1. Egan BM, Basile J, Chilton RJ et al. Cardioprotection: the role of β-blocker therapy. J Clin Hypertens. 2005;7(7):409–16.

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 Diabetes can activate the sympathetic nervous system1,2

Type 2 diabetes

 Insulin resistance

 Insulin

 Norepinephrine release

Ventricular arrhythmias  Plasma renin activity  Angiotensin II

Beta1 adrenergic
stimulation-induced  Intra-glomerular
 BP + non-dipping
cardiac and coronary pressure
at night
artery damage + nephropathy
( atheroma)

Graph adapted from reference 1

1. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton, CT: People's Medical Publishing House-USA;2011; Fig. 3-8
2. Cruickshank JM. Beta-blockers and diabetes: the bad guys come good. Cardiovasc Drugs Ther. 2002;16(5):457–70.
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 Sympathetic activity is elevated in patients with diabetes and hypertension1,2

p<0.001
p<0.001
110
p<0.01
Sympathetic activity (impulses/100 beats)

100
p<0.001
90

80

70

60

50

40

30

20

10

0
EHT+DM EHT DM NT

Essential hypertension (EHT) Type 2 diabetes mellitus (DM) Normotensives (NT)

Graph adapted from reference 1

1. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton, CT: People's Medical Publishing House-USA;2011; Fig. 3-6
2. Huggett RJ, Scott EM, Gilbey SG et al. Circulation. 2003;108:3097–101.
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 Stress activates the sympathetic nervous system1

Acute mental stress

 Corticotropin-releasing hormone
 Endothelin-1
 Cell adhesion Contribution to
 Cortisol  Vasodilation perfusion
Temporary in response to
 Nitric oxide bioavailability endothelial limitation and
chemical and ischemia
 Reactive oxygen species dysfunction mechanical
 Blood glucose and free fatty acids stimuli
 Endothelin-1
If chronically repeated
 Pro-inflammatory cytokines
Increased
 Sympathetic nervous system activation Temporary
risk of
attenuation of
Effect on alpha- and cardiovascular
vasoprotection
beta- adrenergic receptors disease

Graph adapted from reference 1

1. Poitras VJ, Pyke KE. The impact of acute stress on vascular endothelial function: Evidence, mechanisms and importance. Int J Psychophysiol. 2013;88(2):124–35.

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 Obesity activates the sympathetic nervous system1

Central obesity (central adipocytes)

 Production of  Endothelial
vasculotoxic adipokinins  Production of leptin
inflammatory response
(e.g. TNF-alpha, IL-6)

Endothelial dysfunction
and insulin resistance

 Production of insulin

 Norepinephrine release

Sympathetic nervous system activation

Graph according to reference 1

1. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton, CT: People's Medical Publishing House-USA;2011

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 Obesity is associated with increased sympathetic nerve activity1,2

p<0.01

p<0.05
(bursts per min corrected for heart rate)

65
Muscle sympathetic nerve activity

55

p<0.05
45

35

25
Lean Peripherally obese Centrally obese

Graph adapted from reference 1

1. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton, CT: People's Medical Publishing House-USA;2011; Fig. 3-4
2. Grassi G, Dell’Oro R, Facchini A et al. Effect of central and peripheral body fat distribution on sympathetic and baroreceptor function in obese normotensives.
J Hypertens. 2004;22:2363–69.
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 Smoking can stimulate the sympathetic nervous system1

Smoking

Nicotine

Stimulation of sympathetic ganglia

Release of norepinephrine

Vasoconstriction

Increase in peripheral resistance

Increase in heart rate and blood pressure

Graph according to reference 1

1. Klein LW, Pichard AD, Holt J et al. Effects of chronic tobacco smoking on the coronary circulation. J Am Coll Cardiol. 1983;1(2 Pt 2):421–26.
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 Smoking is associated with a two- to three-fold increase in norepinephrine
levels1,2
Smoking
Sham-smoking
Smoking periods
350
Norephinephine (pg/mL)

300 150

Epinephrine (pg/mL)
250 100

200 50

150 0

-10 0 10 20 30 -10 0 10 20 30
Minutes Minutes

Graph adapted from reference 1

1. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton, CT: People's Medical Publishing House-USA;2011; Fig. 3-11
2. Cryer PE, Haymond MW, Santiago JV et al. Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events.
contents N Engl J Med. 1976;295(11):573–7.
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 Conclusions

• Sympathetic overdrive plays a key role in the pathophysiology of

cardiovascular disease，including hypertension，CAD and heart
failure
• Diabetes, Stress, Obesity and Smoking can activate the sympathetic
nervous system

IDN/CONCO/0319/0012

contents
 THANKS FOR YOUR ATTENTION

IDN/CONCO/0319/0012