狼疮严重程度与心脏损伤密切相关
Lupus Severity May Contribute Significantly to Heart Damage
柏林——在欧洲风湿病学大会上，英国曼彻斯特大学关节炎研究英国流行病学中心的Sarah Skeoch博士报告称，系统性红斑狼疮(SLE)患者出现心血管事件的风险比Framingham公式预测的风险高6倍。甘油三酯水平、系统性狼疮国际协作组(SLICC)损伤指数提示的狼疮相关损伤、环磷酰胺治疗分别使患者的心血管风险增加了2.6倍、8.6倍和15.7倍。
Skeoch博士称，虽然患者还可能存在其他一些传统的危险因素，但这似乎不能完全解释其增加的心血管风险。慢性炎症等疾病特征或者疾病治疗也可能起到了一定的作用。“我们希望了解风险与疾病之间的相关性，例如狼疮的活动程度如何，随着的时间的推移患者的损伤程度如何，患者是否会出现肾病，患者所接受的治疗是否与心脏病、卒中等心血管事件相关等等。”
这项研究在2000~2003年间确诊SLE的200例患者中，评价了各种危险因素与心脏损伤风险之间的相关性，最终有124例患者完成了随访。所有患者年龄均大于18岁，均为白人女性。在入组前，其狼疮病情经过治疗至少已经稳定了2个月。Skeoch博士说：“这是一组病情相对较好的患者人群。”
基线时，在这124例患者中有12例之前就曾发生过心血管事件。而且，基线时的SLE疾病活动指数(SLEDAI)评分只有1分，提示疾病活动度低；SLICC损伤指数也很低。
患者接受了血液检查和临床评估以确定传统危险因素水平，狼疮疾病活动度以及与狼疮相关的损伤；此外，也接受了与疾病治疗相关的其他指标评价。
5年后，患者应邀返回医院接受相关评估，并记录心血管事件的发生率，包括在此期间发生的冠脉事件、脑血管事件和周围血管疾病。然后，将基线时根据Framingham公式预测的心血管风险与在112例既往无心血管病史的患者中观察到的结果进行对照。
心血管风险高于预期
随访时，患者的平均年龄为56岁，病程大约为16年。在接受了约5年随访的124例患者中，共有12例(9.7%)出现了心血管事件。其中7例出现了冠脉事件，5例出现脑血管事件，1例出现周围血管疾病。Skeoch博士解释道：“有1例患者在随访期内既出现了冠脉事件又发生了脑血管事件。”
在既往无心血管病史的患者中，根据Framingham公式预测的心血管事件风险提示，在未来5年内1%的患者会出现心血管事件。“但事实上，我们发现7%的患者都出现了心血管事件，比预期水平高6倍。风险高于预期很可能与没有捕捉到的传统危险因素或者疾病本身有关，后者的可能性更大。”
研究者分析了心血管事件的独立危险因素，无论患者是否还存在其他危险因素。结果显示，甘油三酯水平是唯一的传统危险因素，比值比 (OR) 为3.61 (95%置信区间，1.23~10.56)。而Skeoch博士指出，甘油三酯水平往往并非降脂治疗的主要目标，通常是以降低总胆固醇或胆固醇比值为目标。
与心血管事件相关的其他基线特征多因素分析显示，还有2项因素会使患者发生心血管事件的风险增加：SLICC损伤评分(OR，9.62；CI，1.46~63.5)和环磷酰胺治疗(OR，16.7；CI，1.46~123)。Skeoch博士说：“与患者狼疮疾病相关的因素包括患有静脉血栓栓塞、既往出现过与SLE相关的损失、环磷酰胺暴露量以及基线时类固醇用药剂量大，这些都会增加患者出现心血管事件的风险。”
疾病严重程度的标志
Skeoch博士解释道：“这是环磷酰胺治疗首次被视为心血管风险的独立预测因子。我们认为问题并不在于环磷酰胺本身，因为该药可治疗多种疾病，目前也没有证据提示该药会导致心脏病，而关键在于使用环磷酰胺可能提示患者病情严重。此外，使用了环磷酰胺的患者往往类固醇的用药剂量也更大。”
“我们发现SLE患者的心血管疾病风险高于预期，病情严重的患者风险尤其高。我们应当努力监测并管理好传统的危险因素，尽可能地控制SLE疾病活动度以降低患者的心血管风险。”
Skeoch博士声明无相关利益冲突。她接受了英国医学研究理事会提供的研究经费。
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By: BECKY McCALL, Cardiology News Digital Network
BERLIN – The risk of cardiovascular events in patients with systemic lupus erythematosus is sevenfold higher than the risk predicted by the Framingham equation, a study shows.
The role of risk factors varies widely, with the presence of high triglyceride levels upping the risk nearly fourfold while use of cyclophosphamide, which may be a proxy for disease severity, raises the risk almost 17-fold, Dr. Sarah Skeoch, a clinical research fellow at the Arthritis Research UK Epidemiology Unit at the University of Manchester, England, said at the annual European Congress of Rheumatology.
The research also showed that triglyceride level was the only independent traditional risk factor, with a 3.6-fold increased risk association. Damage related to lupus, according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index, increased risk 10-fold. Cyclophosphamide therapy was associated with a 16.7-fold increase in risk.
Although the patients have more of the classical risk factors, this does not seem to account for all the increased risk. Disease characteristics such as chronic inflammation or treatments may contribute, she suggested.
"We wanted to look at the association between risk and disease, for example, how active their lupus is, damage accrued over time, whether they have renal disease, and also whether their treatments are associated with CV events like heart disease and stroke," Dr. Skeoch added.
The study looked at these factors in 200 patients who were diagnosed between 2000 and 2003.
At baseline, 12 patients of the eventual 124 who were followed up had experienced a prior CV event. Also at baseline, the SLE disease activity index (SLEDAI) score was 1, indicating low disease activity, and the SLICC damage index was low.
All patients included in the study were over 18 years of age, female, and white. Their lupus was stable with therapy for at least 2 months prior to inclusion in the study. "They were a relatively well population of patients," said Dr. Skeoch.
Blood tests and clinical assessments were carried out to determine levels of traditional risk factors, lupus disease activity, and lupus-related damage, as well as measurements related to disease therapies.
After a 5-year interval, patients were invited back for assessments and the incidence of CV events, including coronary events, cerebral events, and peripheral vascular disease over the elapsed time period, was recorded.
Next, a comparison was made between the predicted CV risk at baseline according to the Framingham equation and the observed results in 112 patients with no prior CV disease.
CV Risk Higher Than Expected
Upon follow-up, patients were, on average, 56 years old and had had disease for approximately 16 years. Out of the 124 patients followed up over approximately 5 years, 12 (9.7%) had a CV event. Coronary events accounted for seven of these, cerebrovascular events were recorded in five patients, and peripheral vascular disease occurred in one patient. "One patient had both a coronary event and a cerebral event within the follow up," Dr. Skeoch said.
In those who had no prior CV event at baseline, predicted risk of a CV event according to the Framingham equation suggested that 1% of patients should have an event in the next 5 years. "In fact, we found 7% had an event – so seven times higher than predicted. This excess risk is most likely attributed to uncaptured traditional risk factors or alternatively, the disease itself, which is more likely," she commented.
The investigators looked at independent risk factors for a CV event regardless of which other risk factors a patient had and found that triglyceride levels were the only traditional risk factor, with an odds ratio (OR) of 3.61 (95% confidence interval, 1.23-10.56). Triglyceride levels often were not the primary target of lipid-lowering therapy, which was usually aimed at reducing total cholesterol or cholesterol ratio, she noted.
Other multivariable analyses of baseline characteristics associated with CV events suggested that the risk was elevated by two factors: the SLICC damage score (OR, 9.62; CI, 1.46-63.5) and cyclophosphamide therapy (OR, 16.7; CI, 1.46-123). "Factors associated with the patients’ lupus disease included having had a venous thromboembolism, damage related to SLE in the past, cyclophosphamide exposure, and a higher steroid dose at baseline which predisposed the patient to having an event," Dr. Skeoch said.
Marker for Disease Severity
"This is the first time cyclophosphamide [therapy] has been marked as an example of an independent predictor of CV risk. We don’t think it is the cyclophosphamide itself because it has been used in a number of diseases and there’s no known evidence to suggest it causes heart disease, but we think it is a measure of people with severe disease. Also, patients exposed to cyclophosphamide tend to have had more steroids," she explained.
If patients with lupus had severe disease, then they might be more likely to be at risk of CV events in the future, she concluded. "We have found that patients with SLE are at higher risk than expected of CV disease and that those with severe disease may be most at risk. We should endeavor to monitor and treat traditional risk factors and aim for good control of SLE disease activity in order to minimize this risk."
Dr. Skeoch has no relevant conflicts of interest. She is funded by the UK Medical Research Council.
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学科代码：内科学 心血管病学 神经病学 风湿病学 关键词：欧洲风湿病学大会 系统性红斑狼疮患者的心血管事件风险
来源： EGMN
来源： EGMN
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