载脂蛋白和抗磷酸胆碱抗体的纵向水平与类风湿关节炎发病 5 年后颈动脉粥样硬化独立相关——一项前瞻性队列研究。

Longitudinal levels of apolipoproteins and antibodies against phosphorylcholine are independently associated with carotid artery atherosclerosis 5 years after rheumatoid arthritis onset--a prospective cohort study.

机构信息

Department of Rheumatology, R92, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden.

出版信息

Rheumatology (Oxford). 2011 Oct;50(10):1785-93. doi: 10.1093/rheumatology/ker204. Epub 2011 Jul 9.

DOI:10.1093/rheumatology/ker204

PMID:21743088

Abstract

OBJECTIVE

RA is associated with premature atherosclerosis. Here, we determined the associations of apolipoproteins and immunoglobulin M (IgM) antibodies against phosphorylcholine (anti-PC) with carotid artery atherosclerosis in a prospective cohort of patients with early RA.

METHODS

In all 114 patients, age 50.6 (11.2) years, 68.4% women, with recent RA (<12 months after symptoms onset) were included and assessed at 0, 3, 12, 24 and 60 months after RA diagnosis. At the same time points, apolipoproteins were determined by immunoturbidimetry, and IgM anti-PC by ELISA. Carotid intima-media thickness (cIMT) (common carotid) and occurrence of plaques (common, internal and external carotids) were the principal study outcomes, which were examined with high-resolution B-mode ultrasonography after 5 years of RA disease. Mixed linear modelling and generalized estimating equations (GEEs) were used for longitudinal statistical analyses.

RESULTS

Multivariate regression analyses showed that age, male gender, smoking (ever) and history of cardiovascular disease (CVD), hypertension or diabetes mellitus, but no other baseline variables, had independent associations with cIMT (P < 0.05). Plaque detection was positively associated with age and smoking (ever). After adjustment, a longitudinal approach demonstrated an independent negative prediction of cIMT by apoA1 (P = 0.047), but a positive by apoB/apoA1 ratio (P = 0.030). Higher levels of pro-atherogenic apolipoproteins over time, apoB and apoB/apoA1 ratio, and low anti-PC tertile were independently associated with enhanced detection of bilateral carotid plaque (P = 0.002, 0.026 and 0.000, respectively). Both baseline and longitudinal levels of inflammatory/disease-related factors failed to show significant associations with the study outcomes.

CONCLUSION

Apolipoproteins and anti-PC may have independent roles in subclinical atherosclerosis in patients with RA.

摘要

目的

类风湿关节炎（RA）与早发动脉粥样硬化相关。在此，我们在一个早期 RA 患者的前瞻性队列中，确定载脂蛋白和针对磷酸胆碱的免疫球蛋白 M（IgM）抗体（抗-PC）与颈动脉粥样硬化的相关性。

方法

共纳入 114 例年龄 50.6（11.2）岁、68.4%为女性、近期 RA（症状发作后<12 个月）患者，在 RA 诊断后 0、3、12、24 和 60 个月进行评估。在相同时间点，通过免疫比浊法测定载脂蛋白，通过 ELISA 测定 IgM 抗-PC。颈动脉内膜中层厚度（cIMT）（颈总动脉）和斑块（颈总、颈内和颈外动脉）的发生是主要的研究结果，在 RA 发病 5 年后通过高分辨率 B 型超声进行检查。采用混合线性模型和广义估计方程（GEEs）进行纵向统计分析。

结果

多变量回归分析显示，年龄、男性、吸烟（曾）和心血管疾病（CVD）、高血压或糖尿病病史与 cIMT 具有独立相关性（P<0.05）。斑块检出与年龄和吸烟（曾）呈正相关。校正后，纵向分析显示 apoA1 对 cIMT 具有独立的负预测作用（P=0.047），而 apoB/apoA1 比值具有正预测作用（P=0.030）。随着时间的推移，促动脉粥样硬化载脂蛋白水平升高、apoB 和 apoB/apoA1 比值升高、低抗-PC 三分位数与双侧颈动脉斑块检出率升高独立相关（P=0.002、0.026 和 0.000）。基线和纵向炎症/疾病相关因素均与研究结果无显著相关性。