瑞舒伐他汀可减轻系统性硬化症内皮功能障碍

柏林(EGMN)——在欧洲风湿病学大会(ECR)年会上，匈牙利德布勒森大学的Gabriella Szucs博士报告了首个瑞舒伐他汀治疗系统性硬化症(SS)的研究结果：6个月的瑞舒伐他汀(可定)治疗可显著减轻SS患者内皮功能障碍并降低C-反应蛋白(CRP)水平。

目前对病情持续进展的SS患者病尚无基础用药或缓解病情的治疗药物。内皮功能障碍是SS发病机制的第一步，如果能够改善内皮功能则有可能减缓疾病进展，若任其恶化则血管并发症可导致临床症状出现。为此，研究者正在探索他汀类治疗是否能够改善内皮和大血管功能以及动脉硬化程度。

在这项病例系列研究中， 28例入组患者均符合美国风湿病学会(ARA)SS诊断标准。绝大部分(25/28)为女性，平均病程略超过13年。21例为局限性(多见于女性患者)，7例为皮肤受累。受试者入组前6个月均未接受任何他汀类治疗，所有患者在6个月的研究期间均接受20 mg/d的瑞舒伐他汀治疗。患者入组时服用的其他药物包括ARB/ACE抑制剂(75%)、钙离子通道阻滞剂(57%)以及乙酮可可碱(82%)。患者在瑞舒伐他汀前后行血管功能检查和甘油三酯、总胆固醇、低密度脂蛋白(LDL)胆固醇以及CRP等实验室指标检查。

结果显示，变化最明显的是血流介导的血管扩张(FMD)功能改善，FMD由治疗前的2.2%±3.1%提高至治疗后的5.7%±3.8%(正常水平为8%)，28例患者中有23例耾动脉FMD改善显著 (82%)。大动脉硬度(主-股动脉和颈-股动脉脉搏波传导速度)未见变化。但研究者指出，如果疗程延长，该指标有可能发生变化。研究者计划对受试者随访至12月或更长时间。

CRP指标也呈现好转，CRP水平由5.1±5.2 mg/L降至3.4±2.7 mg/L(P=0 .01)。研究者称，多数患者CRP水平已处于正常范围内，但更低的CRP水平对患者更有益，可使心血管疾病发病率和死亡率进一步下降。此外，6个月治疗后LDL水平由3.0±1.3 mmol/L降至2.2±1.0 mmol/L(P=0.005)，平均甘油三酯水平由1.7±0.97 mmol/L降至1.3±0.46 mmol/L(P=0.0004)。局限性或弥散性皮肤受累患者比例未见变化。

研究者认为，SS本质上属于血管疾病，瑞舒伐他汀可改善内皮功能，纠正血脂异常并降低CRP水平。上述结果提示，患者在整个病程中应合用他汀类和常规血管扩张药物，以预防小血管和大血管损伤及并发症。

研究者报告无相关利益冲突。

BY BECKY MCCALL
Elsevier Global Medical News
Breaking News

BERLIN (EGMN) – A 6-month course of rosuvastatin (Crestor) significantly lessened endothelial dysfunction and lowered levels of C-reactive protein in patients with systemic sclerosis, judging from findings from a new study presented at the annual European Congress of Rheumatology.

Dr. Gabriella Szucs of the department of rheumatology, University of Debrecen, Hungary, presented results from the first study of rosuvastatin therapy in systemic sclerosis (SSc), measuring the extent of endothelial dysfunction and response to the drug in the small and large vessels of these patients.

The most significant results were seen in flow-mediated dilatation (FMD), which improved from 2.2% plus or minus 3.1% to 5.7% plus or minus 3.8% (P = .0033) over the 6 months of rosuvastatin therapy. A normal level of FMD would be 8%.

The Hungarian researcher said she and her colleagues wanted to find out whether statin therapy improved the endothelial and macrovascular function as well as arterial stiffness. “These patients had systemic sclerosis with continuous progression for which we don’t even have basic therapy or so-called disease-modifying therapy. We need to try everything to see if something works or not,” said Dr. Szucs, the principal investigator.

“Endothelial dysfunction is one of the first steps in the pathogenesis of the disease. If we can improve this step, it is possible that we can slow disease progression, but if this is allowed to worsen then vascular complications lead to clinical symptoms.”

All 28 patients who entered the case series study had SSc, according to American College of Rheumatology criteria. The majority (25/28) were female, and average disease duration was just over 13 years. The limited form of SSc, which is most common in females, was present in 21 patients, and 7 had the cutaneous form. Patients included had not received any statin medication for 6 months prior to the study. All patients received 20 mg of rosuvastatin daily for the 6 months of the case-series study.

Other therapies used by patients, and on which they were stable at entry to the study, included ARB/ACE inhibitors (75%), calcium channel blockers (57%), and pentoxifylline (82%).
患者服用其他药物包括ARB/ACE抑制剂(75%)、钙离子通道阻滞剂(57%)以及乙酮可可碱(82%)，入组时稳定。
Vascular and laboratory parameters were checked both before and after rosuvastatin therapy, including triglycerides, total and low-density lipoprotein (LDL) cholesterol, and C-reactive protein (CRP) levels.

Notably, brachial artery flow-mediated dilatation significantly improved in 23 of the total of 28 patients (82%). “For stiffness in the larger arteries [pulse-wave velocity of the aorto-femoral and carotid-femoral] we didn’t see any changes but this might vary if treatment continues for longer. We intend to follow these patients up at 12 months and thereafter.”

She added that CRP levels were also shown to improve. CRP levels dropped from 5.1 plus or minus 5.2 mg/L before treatment to 3.4 plus or minus 2.7 mg/L (P = .01) after 6 months. “They are almost in the normal range, but it is better for the patient to have a lower CRP because later cardiovascular morbidity and mortality can decrease.”

As expected, LDL levels decreased over the 6 months from 3.0 plus or minus 1.3 mmol/L to 2.2 plus or minus 1.0 mmol/L (P = .005), and mean triglyceride levels dropped from 1.7 plus or minus 0.97 mmol/L to 1.3 plus or minus 0.46 mmol/L (P = .0004).

No difference was seen between the limited form or the diffuse cutaneous form, reported Dr. Szucs.

“Systemic sclerosis is basically a vascular disease and rosuvastatin may improve endothelial dysfunction, correct dyslipidemia, and decrease CRP levels,” said Dr. Szucs. “These results suggest that statins should be used together with more conventional vasodilator therapy throughout the disease course in order to protect from micro- and macrovascular damage and complications in scleroderma.”

Dr. Szucs has declared no relevant conflicts of interest.