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JOHN LEKAKIS , MD , FESC ASSOCIATE PROFESSOR OF
CARDIOLOGY ATTIKON UNIVERSITY HOSPITAL
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• Psoriasis is the most common immune-mediated skin
  disease with an estimated prevalence of 23
• Psoriatic arthritis, a chronic inflammatory
  arthropathy, is present in about 11 of people
  with psoriasis with wide variability reported.
• A substantial proportion of patients have
  polyarthritis.

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• that a pro-inflammatory stimulus leads to the
  formation of immunological synapses between
  dendritic and T cells with subsequent
  antigen-specific T cell activation.
• The resultant release of cytokines, chemokines
  and growth factors initiates the proliferation
  and altered differentiation of keratinocytes and
  further enhances the activation of T cells and
  antigen-presenting cells (APCs), particularly
  dendritic cells, within the psoriatic plaque

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GhazizadehInt. J. Med. Sci. 2010, 7
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Dermatologic Therapy, Vol. 23, 2010, 144151
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Kimball Dermatology 20082172737
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Psoriasis CVDR risk compared to controls. Odds
ratios (OR) and confidence intervals (CI) based
on a unique patientcount of those having 1 or
more medical claims within the period. CVD
Cerebrovascular disease CHF congestive
heart failure DMT2 type 2 diabetes
mellitusHTN hypertension IHD ischemicheart
disease AMI acute myocardial infarctionPVD
peripheral vascular disease.
Kimball Dermatology 20082172737
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Gelfand JM,JAMA. 20062961735-1741
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Summary

• Psoriasis appears to be an independent risk
  factor for CAD.
• The risk is greatest in those with severe
  psoriasis.
• There is an Inverted Risk for Age, that is,
  psoriasis is a greater risk factor for CAD in the
  younger population.

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Associated Conventional Risk Factors
Patients
JAMA 2006141735
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Conventional Risks

• Blood Pressure Control
• Smoking Cessation
• Aggressive Lipid Therapy
• Glucose Control

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Disease Specific Therapy

• Does disease specific therapy for psoriasis
  reduce the risk for future cardiac events?
• No current large scale trials investigating this
  question.
• In order to study effect of disease specific
  therapy on cardiac risk, we need a method for
  detecting early CAD.

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Coronary Endothelium

• Function
• Regulation and prevention of thrombosis.
• Regulation of vasomotor tone and coronary blood
  flow.

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Venous occlusion plethysmography
Cuff inflator
Data acquisition and analysis
Intra-arterial infusion
Plethysmograph
BP and HR monitoring
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BRACHIAL FLOW MEDIATED DILATION
High Resolution Ultrasound
Endothelium-independent response ? diameter of
the brachial artery after GTN (s.l.)
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NO-DEPENDENT FLOW MEDIATED DILATION
FMD (D)
saline
L-NMMA
Time after ischemia (sec)
Ghiadoni L et al. J Hypertens 2007
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PULSE AMPLITUDE TONOMETRY
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Clinical Consequences of Endothelial Dysfunction

• Coronary Endothelial Dysfunction is clearly
  associated with adverse cardiac events.
• May be considered a marker for early CAD

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Endothelial DysfunctionIn Patients with Psoriasis
P lt 0.04
Flow Mediated Dilation ()
Arthritis Care Research 200757287
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BUT..after exclusion of patients with risk
factors, no significant difference in endothelial
function was observed Martyn-Simmons CL et al ,
Br J Dermatol 2011 , 164 26-32
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Young compliant arteries Normal PW velocity (8
m/sec)
Systole
Diastole
(1) Ventricular-Vascular coupling (2) ? coronary
blood flow
Systole
(1) Ventricular-vascular mismatch (2) The
reflected wave increases or augments central
SBP during late systole

• Increases vascular afterload with a
  propensity to develop LVH Decreases coronary
  perfusion pressure
• Increases myocardial oxygen demand and
  subendocardial ischemia
• Increases flow turbulence, endothelial
  dysfunction and atherogenesis
• Increases in pulsatile strain and chance of
  plaque rupture
• All recognized by a wide brachial artery pulse
  pressure in the elderly

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AORTIC ELASTIC PROPERTIES
elastic aorta
stiff aorta
ORourke M. Arterial function in health and
disease. Churchill Livingstone 1982
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Yiu KH Br J Dermatol. 2010 Oct 29
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• Young patients with psoriasis have increased
  arterial stiffness
• but not microvascular dysfunction compared with
  healthy controls.
• More importantly, hs-CRP positively correlated
  with, and independently predicted, arterial
  stiffness.
• This suggests systemic inflammation in patients
  with psoriasis is associated with premature
  atherosclerosis.

Yiu KH Br J Dermatol. 2010 Oct 29
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Kimhi H,Semin Arthritis Rheum 36203-209
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• HOMA-IR was significantly higher in patients with
  psoriasis than in controls.
• (2.1 (0.868.9) vs. 1.8 (0.68.6), P  0.036)
• FMD was reduced in patients with psoriasis
  compared with healthy controls
• (5.6  1.9 vs. 10.9  1.9, P lt 0.001).

Karadag AS, Int J Dermatol. 2010 Jun49(6)642-6
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ECONOMY
Ok. We Have a Problem, But What Do We Do About
it?
Therapy and Prevention
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• Disease-modifying antirheumatic drugs (DMARDs)
• Biological agents targeting tumour necrosis
  factor (TNF) a are effective in psoriatic
  arthritis
• However, some individuals
• are not responsive to these treatments, do not
  maintain a clinical response (defined by 20
  improvement from baseline in the American College
  of Rheumatology ACR20 core set measures),
• or have contraindications or intolerance to
  anti-TNF agents

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Griffiths, JEADV 2010
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Kimball A Arch Dermatol. 2008144(2)200-207
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(No Transcript)
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Group 1 ustekinumab every week for 4 weeks
(weeks 03) followed by placebo at weeks 12 and
16 (n76)
Group 2 placebo (weeks 03) and ustekinumab at
weeks 12 and 16 (n70).
Lancet 2009 373 63340
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ACCEPT Study Group N Engl J Med 2010362118-28.
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(No Transcript)
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Goedkoop et al.Arthritis Res Ther 2004,
6R326-R334
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Goedkoop et al.Arthritis Res Ther 2004,
6R326-R334
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Systemic therapy with fumaric acid esters
improved systemic endothelial function assessed
by venous occlusion plethysmography 13
patients Boehncke S et al , Arch Dermatol Res
2010, Dec 18
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Hypertension. 201055333-338.)
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CHRONIC PHASE
3 MONTHS
USTEKINUMAB
n25
GROUP A?
ETANERCEPT
n25
GROUP B
NON BIOLOGICAL AGENTS
n25
GROUP B
0
3 MONTHS
ARTERIAL STIFFNESS (PWV,AI,)
OXIDATIVE STRESS ENDOTHELIAL FUNCTION (FMD)
INFLAMMATORY CYTOKINES CAROTID IMT
Lp-PLA2 CORONARY FLOW RESERVE LV FUNCTION
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• THANK YOU