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Abstract Number: 699

Endothelial Dysfunction and Vascular Stiffness in Early Diffuse Systemic Sclerosis

Robyn T. Domsic1, Dana Ivanco2, Hunter C. Champion3, Ali Shoushtari3 and Thomas A. Medsger Jr.4, 1Medicine - Rheumatology, University of Pittsburgh, Pittsburgh, PA, 2Department of Medicine/Div. of Rheumatology, University of Pittsburgh, Pittsburgh, PA, 3Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, 4Medicine/Rheumatology, Univ of Pittsburgh, Pittsburgh, PA

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Cardiovascular disease, endothelial cells and systemic sclerosis

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Session Information

Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud’s – Clinical Aspects and Therapeutics

Session Type: Abstract Submissions (ACR)

Background/Purpose: Vascular dysfunction is a hallmark of systemic sclerosis (SSc).  Current theories postulate endothelial injury and dysfunction as an early event in SSc pathogenesis.   Prior cross-sectional studies suggest endothelial dysfunction and increased vascular stiffness in SSc, but generally use longstanding patients.  Our aim was to measure and describe endothelial function and vascular stiffness in an inception cohort of early diffuse SSc patients.

Methods: Early diffuse SSc was defined as < 2 years from the first symptom attributable to SSc and skin thickening proximal to the elbows or knees.   SSc patients were matched 1:1 with age (± 2 years), gender and race matched healthy controls.  Vasodilators were held for 24 hours.    Aortic pulse wave velocity (PWV) was used to assess vascular stiffness by averaging two measures recorded simultaneously at the carotid and femoral arteries. In a quiet and temperature controlled exam room, all underwent assessment of endothelial function with three validated methods:  1) assessment of endothelial-dependent flow-mediated dilation (FMD)  by ultrasound before and after reactive hyperemia (RH) of the medium-sized brachial artery induced by pneumatic cuff for 5 minutes; 2) endothelial-independent vasodilation of the brachial artery before and after nitroglycerin (NTG); 3) assessment by Endo-PATTM, which measures the pulse wave amplitude before and after RH using a pneumatic probe on the index finger.  FMD was expressed as % change in diameter after RH and NTG.  EndoPAT calculates a reactive hyperemia index (RHI), with a RHI of < 1.67 previously validated as the cut-off for endothelial dysfunction. Differences in PWV, FMD, NTG and RHI were assessed by paired t-tests.  

Results: 16 early diffuse SSc patients were compared to  16 age, gender and race-matched  controls.    The mean age in cases was 48.9 years (controls 48.2), 56% were female, 94% Caucasian and 6% Asian.  The median disease duration at time of vascular study was 1.2 years (0.9, 1.8), and the mean modified Rodnan skin score 20.8 ± 8.3.  86% of patients experienced Raynaud phenomenon, 37% had digital pitting scars and none had renal crisis.   69% were on immunosuppressive agents.   There was no difference in PWV between patients (6.58 ± 1.40) compared to controls (6.28 ± 1.04; p=0.67).  The median FMD % change after RH was not significantly different in cases and controls (4.6% ±5.1 vs 5.0%±5.3; p=0.10), or after NTG administration (p=0.90).  However, there was a significant difference in EndoPAT RHI of 1.20 (±0.56) for patients and 2.06 (±0.52) for controls (p=0.002).  Overall, 80% of patients had abnormal RHI suggesting ED, compared to 20% of controls. 

Conclusion: There is no difference in large vessel vascular stiffness between early diffuse SSc patients and age, gender and race matched controls.  Similarly, there is no difference in brachial-artery FMD to RH or NTG, suggesting no difference in endothelial function of the medium-sized arteries.  However, there was significantly increased endothelial dysfunction of the small arterioles as measured by EndoPAT.  These results suggest that endothelial changes occur in smaller arterioles and microvascular beds in early SSc, but not in macrovascular beds.


Disclosure:

R. T. Domsic,
None;

D. Ivanco,
None;

H. C. Champion,
None;

A. Shoushtari,
None;

T. A. Medsger Jr.,
None.

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