Exploring the potential of cholesterol-lowering drugs for patients with systemic sclerosis

Systemic sclerosis (SSc), also known as scleroderma, is an uncommon and confounding disease characterized by excessive fibrous tissue formation and vascular abnormalities. Primarily affecting the small arties, SSc decreases blood flow to the body's extremities. This can lead to Raynaud's phenomenon, a condition that causes the hands and feet to feel extremely cold and numb; ulcers on the fingers and toes; and gangrene. SSc can also restrict blood flow to internal organs, resulting in lung, kidney, and heart damage. While its cause and cure have yet to be found, SSc is generally viewed and treated as an autoimmune inflammatory disorder.

Researchers in Japan recently proposed a different theory: the root of SSc may be defective vasculogenesis, the process of forming new blood vessels by producing new cells in the blood vessel lining. In the June 2006 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), Dr. Masataka Kuwana and colleagues at the Keio University School of Medicine in Tokyo share the results of an experiment to affirm their hypothesis and test a novel treatment strategy. Their objective: to determine the effectiveness of one of the most popular and potent cholesterol-lowering drugs – atorvastatin, marketed under the brand name Lipitor – for increasing blood flow and improving the symptoms of SSc.

The study focused on 14 women, between ages 36 and 75, with a confirmed diagnosis of SSc. Disease duration ranged from 13 months to 21 years. All the patients were treated with 10 milligrams of atorvastatin per day for 12 weeks; all but one participated in a follow up 4 weeks after. At the time of entry, all the patients had active Raynaud's phenomenon, and 2 had digital ulcers. For the study's duration, all patients continued their routine course of treatment, from low-dose aspirin to low-dose prednisolone.

At pre-treatment, at weeks 4, 8, and 12 during treatment, and at 4 weeks post-treatment, all the patients were evaluated for SSc symptoms. What's more, and most significant, each patient was assessed, using rigorously developed assay systems, for their absolute number of circulating endothelial precursors (CEPs). Vasculogenesis requires the recruitment of CEPs from bone marrow to form blood vessels when there are no pre-existing ones. This study's ultimate goal was to evaluate whether statins work to treat SSc by increasing patient's production of strong, blood vessel-building CEPs.

For the 13 patients who completed the 12 weeks of therapy, atorvastatin yielded a 1.7 to 8-fold increase in the number of CEPs. However, for 8 patients, 62 percent of the group, CEP levels peaked during treatment, either at week 4 or week 8, and gradually decreased thereafter. Even for the 5 patients who experienced continual gains in CEP levels while taking atorvastatin, the numbers did not reach the levels seen in healthy individuals. For all patients, CEP counts returned to within baseline counts by the follow up session. All the patients experienced improvements in Raynaud's phenomenon activity while taking atorvastatin. Symptoms generally returned to within baseline levels after discontinuation of the drug.

As this study demonstrates, atorvastatin is capable of stimulating CEP production in SSc patients. But its effects are limited. "Although the results of this preliminary study are encouraging," Dr. Kuwana notes, "further multicenter, placebo-controlled trails involving a large number of SSc patients are necessary to confirm the clinical benefit of statins in SSc patients."

Article: "Increase in Circulating Endothelial Precursors by Atorvastatin in Patients With Systemic Sclerosis," Masataka Kuwana, Junichi Kaburaki, Yuka Okazaki, Hidekata Yasuoka, Yutaka Kawakami, and Yasuo Ikeda, Arthritis & Rheumatism, June 2006, 54:6, pp. 1946-1951.

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