ICSLE：狼疮患者的心血管风险

　　阿根廷布宜诺斯艾利斯——众所周知，诸如Framingham风险评分之类的传统工具会低估系统性红斑狼疮(SLE)患者的心血管风险。在日前举行的国际系统性红斑狼疮大会上，约翰霍普金斯大学的Michelle Petri博士的报告为一种新的10年心血管事件(CVE)风险估算工具提供了支持。

　　这种新工具综合了传统系血管危险因素(年龄、性别、高血压、高血脂、吸烟、糖尿病和体重指数)与3种狼疮特异因素：SLEDAI(SLE疾病活动度指数)评分≥2、狼疮抗凝物和补体3(C3)平均水平低。

　　例如一名年龄50岁的女性SLE患者，体重指数(BMI)为23 kg/m2、收缩压为150 mmHg、患有高脂血症，那么按照新工具和Framingham评分，其10年CVE风险均为8%左右。然而，假如她还有狼疮抗凝物、高疾病活动度或者C3水平低，则根据SLE特异评分系统其CVE风险将增至15%~18%，而Framingham评分仍为8%。Petri博士指出，假如患者合并类风湿性关节炎，则危险评分还得再乘以1.5。

　　“我们知道，传统心血管危险因素的确可以预测事件，还能预测亚临床动脉粥样硬化的进展。然而即使我们校正所有的传统心血管危险因素，狼疮患者的冠脉钙化风险仍然比对照者增加1倍，因此显然必须将狼疮特异因素纳入评分系统。”

　　这种新评分工具的支持数据来自在约翰霍普金斯狼疮中心接受治疗的1,342例狼疮患者(女性占93%)。无1例患者在随访头2年内发生CVE。在研究期间，这一队列共发生了109例次散发性CVE，包括52例次卒中和26例次心肌梗死。

　　Petri博士及其同事采用Cox比例风险模型来判断影响之后CVE风险的基线变量。根据判断结果，研究者设计出了一项估算10年CVE风险的公式。研究者将每项危险因素的危险比(HR)都转换为简单整数评分，以简化估算，更便于临床应用。通过累加各项危险因素的整数评分和使用取代指数方程的计算尺，临床医生可以找到与总分对应的风险百分率。

　　Petri博士承认这项研究存在一些局限性，包括为单中心设计，约翰霍普金斯狼疮中心并未常规检测血脂，以及这项研究反映的是较早年代的医疗情况。

　　另一项针对狼疮患者CVD风险的多变量分析从土耳其伊斯坦布尔某医院纳入了连续306例SLE患者(平均年龄40.2岁，女性占89%)。分析结果显示，心包炎、淋巴细胞减少、血小板减少和精神病与非致死性CVD显著相关。

　　主要研究者、伊斯坦布尔大学的Murat Inanc博士指出，15.2%的受试者有CVD的临床证据。其中很多人还有传统危险因素，“如高血压、高血脂、代谢综合征等，但疾病特异性表现在心血管受累的患者中也更多见”。

　　有CVD证据的患者年龄更大、病程更长，器官损伤明显更多，而且符合美国风湿病学会(ACR)SLE标准者更多。“我们认为，对于这一人群而言，疾病严重程度几乎与传统危险因素同等重要。”环磷酰胺治疗也被认为是一个危险因素，尽管这一点可能与疾病严重程度有关。

　　Inanc博士承认，这项研究存在一些局限性，包括为单中心设计、缺乏关于亚临床CVD的数据。研究者没有分析皮质类固醇累计用量的影响，也没有采集有关免疫抑制剂使用的信息。

　　多伦多西方研究所的Murray Urowitz博士在本次会议上报告了一项纳入1,401例SLE患者的国际多中心起始队列研究。该研究旨在确定诊断时可预测早发动脉粥样硬化的因素。Urowitz博士及其同事分析了年龄、性别、糖尿病、吸烟、肥胖、低密度脂蛋白胆固醇和肌酐等因素。经过平均5年随访，多变量分析显示，仅有年龄和男性是粥样硬化性血管事件的显著危险因素。“这一结果提示，这些危险因素需要更长时间才能体现出最大效应，而在头10年内其效应很难超过年龄和性别这两个因素。”

　　同样在这场会议上，加州大学洛杉矶分校的Maureen McMahon博士报告称，一些生物标志物可预测SLE患者的当前进展性或获得性颈动脉斑块。在这项研究中，McMahon博士及其同事招募了210例女性SLE患者和100名年龄匹配的对照者，这些受试者在基线时和平均随访29个月之后接受颈动脉超声检查。结果显示，近1/3的SLE患者在随访期间有斑块的证据。

　　研究者发现，如果基线时有下列因素中的至少3项，即可预测94%的斑块：年龄≥48 h，有促炎性高密度脂蛋白胆固醇的证据，血浆瘦素≥34 ng/dl，同型半胱氨酸≥12 mmol/L，血浆sTWEAK(可溶性肿瘤坏死因子样弱凋亡诱导物)水平≥373 pg/ml。上述因素中的任意1项加上糖尿病，也具有预测效力。具有至少3项危险因素(或者1项加糖尿病)的患者，今后出现颈动脉斑块的几率将增加28倍[95%置信区间(CI)，10.6~72.7；P＜0.001]，并且出现斑块和动脉内膜中层厚度进展的几率也显著增加。

与狼疮相关的拓展阅读：

• 狼疮患者的心血管风险
• 系统性红斑狼疮合并血栓性血小板减少性紫癜的临床特点
• Int Med News：重视生物制剂对狼疮的作用
• AJHG：全基因组关联Meta分析搜寻系统性红斑狼疮易感基因
• Arthr Res & Ther：来那度胺或成为治疗皮肤红斑狼疮的有效疗法
• Lupus：血清肿瘤坏死因子-α水平与系统性红斑狼疮患者的生活质量和抑郁症状相关
更多信息请点击：有关狼疮更多资讯

原文阅读：New studies outline cardiovascular risk in lupus patients
BUENOS AIRES – Traditional tools such as the Framingham risk score have long been known to underestimate cardiovascular risk in people with systemic lupus erythematosus.
At the international congress on systemic lupus erythematosus, Dr. Michelle Petri of Johns Hopkins University, Baltimore, presented data in support of a novel risk-assessment formula to calculate the 10-year risk of a cardiovascular event (CVE). The tool combines the traditional cardiovascular disease risk factors of age, sex, high blood pressure, high cholesterol, smoking, diabetes, and body mass index (BMI), with three lupus-specific factors: a SLEDAI (SLE Disease Activity Index) score of 2 or higher, lupus anticoagulant, and a low mean complement 3 (C3) level.
Under both this and the Framingham algorithms, a 50-year old woman with SLE with a BMI of 23 kg/m2, systolic blood pressure of 150 mm Hg, and high cholesterol has about an 8% 10-year risk of a CVE. However, if she also has lupus anticoagulant, high disease activity, or a low C3 level, her risk rises to 15%-18% under the SLE-specific system, whereas her Framingham score, which does not measure these, would remain at 8%.
Dr. Petri told the conference that with rheumatoid arthritis, the advice has been to multiply an existing risk score by 1.5 when the patient has certain evidence of disease. "I thought we could do better than that in lupus, because we could derive a formula using actual data," she said.
"We know that traditional CV risk factors do predict actual events and also predict the progression of subclinical atherosclerosis. Even after we adjust, though, for every traditional cardiovascular risk factor, lupus patients still have a twofold increase in coronary calcium over controls – so obviously lupus-specific factors must be in the formula as well."
The data used to derive the new scoring system came from a cohort of 1,342 lupus patients (93% female) treated at the Johns Hopkins Lupus Center. None had a history of CVEs during the first 2 years of follow-up. Over the study period, 109 incident CVEs occurred in the cohort, including 52 strokes and 26 myocardial infarctions.
Dr. Petri and her colleagues used Cox proportional hazards models to determine the baseline variables affecting the risk of a subsequent CVE. Using the results, they derived a formula to calculate the 10-year risk of a CVE. For each of the risk factors, they investigators converted the hazard ratio into a simple integer score to simplify calculation in clinical practice. By adding up the integers and using a slide rule that stands in for the exponential equation, clinicians can translate the integer score into a risk percentage.
Dr. Petri acknowledged as limitations of the study its single-site design; the fact that the Johns Hopkins Lupus Center does not routinely perform cholesterol screening; and that the study reflects care from 1988 onward, where more recent data could reflect a better standard of care. "This needs to be independently validated," she said.
In another multivariate analysis of cardiovascular disease (CVD) risk factors in lupus, a cohort of 306 consecutive SLE patients at a clinic in Istanbul, Turkey, revealed pericarditis, lymphopenia, thrombocytopenia, and psychosis to be significantly associated with nonfatal CVD.
Dr. Murat Inanc of Istanbul University, the lead author of the study, said that 15.2% of the cohort (mean age, 40.2 years; 89% female) had clinical evidence of CVD. Many of them also had traditional risk factors. "The usual suspects are there – hypertension, high cholesterol, metabolic syndrome – but we also found disease-specific features more present in patients with CV involvement," Dr. Inanc said.
Patients with evidence of CVD were older and had longer disease duration, significantly more organ damage, and a higher number of American College of Rheumatology criteria for SLE. "We think disease severity takes almost equal importance with traditional risk factors in this population," he said. Treatment with cyclophosphamide was also seen as a risk factor, although it is likely related to disease severity, he told the congress.
Dr. Inanc noted that the conclusions that can be drawn from the study are limited by its single-site design and lack of data on subclinical CVD. Cumulative corticosteroid use was not investigated, and investigators did not have information on immunosuppressive use in the cohort.
Dr. Murray Urowitz, of the Toronto Western Research Institute, presented findings from an international, multicenter inception cohort of 1,401 SLE patients. The goal of the study was to determine factors at diagnosis that are predictive of the development of premature atherosclerosis. Dr. Urowitz and his colleagues looked at age, sex, diabetes, smoking, obesity, low-density lipoprotein cholesterol, and creatinine. A multivariate analysis showed that only age and male sex were significant risk factors for atherosclerotic vascular events after a mean 5 years’ follow-up. "The implication here is these risk factors take more time to have their maximum effect, and in the first decade it’s hard to have more than age and sex," Dr. Urowitz told the congress.
Also at the congress, Dr. Maureen McMahon of the University of California, Los Angeles, gave a presentation on a panel of biomarkers found to be predictive of current, progressive, or acquired carotid plaque in a cohort of SLE patients.
For their research, Dr. McMahon and her colleagues looked at 210 female SLE patients and 100 age-matched controls who underwent ultrasound imaging of their carotid arteries at baseline and after a mean 29 months of follow-up. Nearly a third of SLE patients had evidence of plaque on follow-up.
The researchers found that three or more of the following factors at baseline were 94% predictive of plaque: age 48 or older, evidence of proinflammatory high-density lipoprotein cholesterol, plasma leptin of 34 ng/dL or greater, homocysteine of 12 mmol/L or greater, and plasma levels of sTWEAK (soluble tumor necrosis factor–like weak inducer of apoptosis) of 373 pg/mL or greater. Any one of these factors plus diabetes was also predictive. Patients with at least three indicators (or one plus diabetes) saw a 28-fold increased odds for the longitudinal presence of carotid plaque (95% confidence interval, 10.6-72.7; P less than .001) and a significantly increased rate of progression of both plaque and intima-media thickness.
None of the investigators disclosed financial relationships related to these studies.