Effect of Atorvastatin on Endothelial Function and Raynaud in Diffuse Scleroderma

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

? DESCRIPTION: Systemic sclerosis (SSc) is a multisystem autoimmune illness characterized by vasculopathy, immune system activation and fibrosis of the skin and internal organs. SSc affects approximately 240 people per million in the US, but is a disease for which there is no FDA approved medication. Current hypothesis of pathogenesis suggest that a vascular injury with endothelial dysfunction may be an inciting event contributing to immunologic activation and fibrosis in the pathogenesis of the disease. More than 90% of individuals with SSc have vascular complications including Raynaud phenomenon, digital ulcers or gangrene and pulmonary hypertension, with microvascular abnormalities felt to contribute to Raynaud and digital ulcerations. Statin medications are well-recognized to have pleiotropic effects which may modify all aspects of SSc pathogenesis. A few preliminary statin studies have found conflicting results, but have used patients with overall longstanding disease, when the vasculopathy may have not been amenable to treatment. In our preliminary work we have found evidence that statins may mediate microvascular endothelial dysfunction in patients with very early systemic sclerosis. Laser speckle contrast imaging (LSCI) is a newer imaging modality that assesses microcirculation and has been proposed as a surrogate marker for systemic microvascular function. Our preliminary data showed a distinct pattern of microcirculatory flow as measured by LSCI compared to healthy age, gender and race-matched controls and holds promise as a functional assessment of microvascular function in SSc patients. Our hypothesis are that treatment with atorvastatin in a well-defined cohort of early diffuse SSc will improve microvascular endothelial function as measured by EndoPAT and thereby improve related Raynaud symptoms. We propose to apply LSCI imaging as a modality to assess microvascular endothelial function response to statins and hypothesize that this modality will allow us to predict responders to statins.