Lipids, Inflammation, and Cardiovascular Risk in Rheumatoid Arthritis

类风湿性关节炎的脂质、炎症和心血管风险

• 批准号: 9883821
• 负责人: Katherine Phoenix Liao
• 金额: $ 74.52万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883821
• 关键词: Anatomy; Anti-Inflammatory Agents; Anti-Tumor Necrosis Factor Therapy; Apolipoprotein A-I; Apolipoproteins B; Blood; Blood Vessels; Blood specimen; C-reactive protein; Cardiac; Cardiovascular system; Categories; Cholesterol; Clinical; Coronary; Data; Development; Disease; Disease remission; Event; General Population; Heart; Heart Diseases; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Imaging Techniques; Impairment; Inflammation; Injury; Intervention; Knowledge; LDL Cholesterol Lipoproteins; Lead; Link; Lipids; Lipoprotein (a); Lipoproteins; Longitudinal Studies; Low-Density Lipoproteins; Measurement; Measures; Methods; Mission; Myocardial perfusion; National Heart, Lung, and Blood Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Observational Study; Outcome; Particle Size; Patients; Physiological; Positron-Emission Tomography; Prospective Studies; Public Health; Reproducibility; Research; Rheumatism; Rheumatoid Arthritis; Risk Estimate; Risk Factors; Role; Stress; Surrogate Markers; TNF gene; Testing; Time; Troponin T; Vasomotor; arthritis therapy; cardiovascular risk factor; clinically significant; cohort; experimental study; follow-up; heart disease risk; human model; imaging study; improved; inclusion criteria; inflammatory marker; innovation; insight; mortality; myocardial injury; prevent; prospective; public health relevance; recruit; rheumatologist

 DESCRIPTION (provided by applicant): Patients with rheumatoid arthritis (RA) are at 1.5x risk for heart disease risk compared to the general population. Effective RA therapies which reduce inflammation such as tumor necrosis factor antagonists (anti- TNF), increase levels of low density lipoprotein cholesterol (LDL-C) suggesting that treatment may increase the burden of heart disease. However, large observational studies suggest the opposite: anti-TNF therapies are independently associated with reduced heart disease risk. While inflammation may explain these seemingly paradoxical findings, the exact mechanisms are poorly understood. A gap in knowledge exists regarding how rheumatologists should weigh changes in lipid levels with treatment and level of inflammation when assessing for risk of heart disease in RA. The objective of this proposal is to determine the clinical significance of increased LDL-C levels in associated with reduction in inflammation by anti-TNF therapy, and directly test the association of changes in inflammation with changes in lipid levels and risk of heart disease. The central hypothesis of this study is that reducing inflammation will be associated with reduced heart disease risk in RA. We will further determine whether advanced lipoprotein measures, including apolipoprotein B and A1 levels, LDL particle size and HDL function may be better markers of heart disease risk in RA patients. The Aims of this project are to: (1) study the longitudinal association between changes in inflammation with changes in advanced lipoprotein measures, (2) determine the effect of reducing inflammation with anti-TNF therapy on markers of injury and vascular function in the heart, (3) examine the effect of reducing inflammation on changes in advanced lipoprotein measures, and association with heart disease risk in RA. Aim 1 will be conducted using data and blood samples collected annually from a prospective longitudinal RA cohort. Subjects (N=200) with significant changes in inflammation between two consecutive years will be identified and their blood samples measured for inflammatory markers, lipids and advanced lipoprotein tests. In Aims 2 and 3, RA patients (N=75) about to initiate anti-TNF therapy will be recruited, and prospectively studied for changes in inflammatory markers, routine lipids and advanced lipoprotein measures before and at 6, 12, and 24 weeks after starting anti-TNF. Subjects will undergo cardiac PET imaging to calculate coronary flow reserve (CFR) at baseline and 24 weeks. CFR measures coronary vascular function and is a validated surrogate marker for heart disease risk. This approach is innovative because it leverages RA as a human model of inflammation. In this experiment anti-TNF is repurposed as an intervention to reduce inflammation in order to study associated changes in lipids and risk for heart disease. The study is significant because it may transform the way heart disease risk is assessed in RA, by informing development of an integrated approach using comprehensive lipid measurements and level of inflammation. Results from this study may also have implications for the general population where inflammation has a smaller but significant role in the risk of heart disease.

 描述（由申请人提供）：与普通人群相比，类风湿性关节炎 (RA) 患者患心脏病的风险是普通人群的 1.5 倍。有效的 RA 疗法可减少炎症，例如肿瘤坏死因子拮抗剂（抗 TNF）、增加 TNF 水平。低密度脂蛋白胆固醇 (LDL-C) 表明治疗可能会增加心脏病的负担，然而，大型观察性研究表明相反的情况：抗 TNF 疗法与降低心脏病风险独立相关，而炎症可以解释这些。看似矛盾的发现，对于风湿病学家在评估 RA 心脏病风险时应如何权衡血脂水平与治疗和炎症水平的变化，人们对确切的机制知之甚少。 LDL-C 水平升高与抗 TNF 治疗减少炎症相关的临床意义，并直接测试炎症变化与脂质水平变化和心脏病风险的关联。本研究的中心假设是减少炎症。与 RA 心脏病风险降低有关。我们将进一步确定高级脂蛋白测量（包括载脂蛋白 B 和 A1 水平、LDL 颗粒大小和 HDL 功能）是否可能是 RA 患者心脏病风险的更好标记。该项目的目的是：（1）研究之间的纵向关联。炎症随着高级脂蛋白测量值的变化而变化，(2) 确定抗 TNF 治疗减少炎症对心脏损伤标志物和血管功能的影响，(3) 检查减少炎症对高级脂蛋白测量值变化的影响， 和目标 1 将使用每年从前瞻性纵向 RA 队列中收集的数据和血液样本来进行，将确定连续两年之间炎症发生显着变化的受试者（N = 200）并测量他们的血液样本。在目标 2 和 3 中，将招募即将开始抗 TNF 治疗的 RA 患者 (N=75)，并前瞻性研究炎症标志物、常规血脂和晚期脂蛋白的变化。这种方法是创新的，因为它利用 RA 作为人类炎症模型，在该实验中，抗 TNF 被重新用作减少炎症的干预措施。研究血脂的相关变化和心脏病风险这项研究意义重大，因为它可能会改变评估 RA 心脏病风险的方式，通过使用全面的脂质测量和炎症水平来开发综合方法，该研究的结果也可能对患有炎症的一般人群产生影响。对心脏病风险的影响虽小但很重要。

项目成果

Lipids in RA: Is Less Not Necessarily More?

• DOI: 10.1007/s11926-018-0715-7
• 发表时间: 2018-02-01
• 期刊: CURRENT RHEUMATOLOGY REPORTS
• 影响因子: 5
• 作者: Plutzky, Jorge;Liao, Katherine P.
• 通讯作者: Liao, Katherine P.

Interference of tumor necrosis factor inhibitor treatments on soluble tumor necrosis factor receptor 2 levels in rheumatoid arthritis.

肿瘤坏死因子抑制剂治疗对类风湿性关节炎可溶性肿瘤坏死因子受体 2 水平的干扰。

• DOI: 10.1016/j.plabm.2019.e00122
• 发表时间: 2019
• 期刊: Practical laboratory medicine
• 影响因子: 1.9
• 作者: Yang,Nicole;Huang,Jie;Frits,Michelle;Iannaccone,Christine;Weinblatt,MichaelE;Rifai,Nader;Shadick,Nancy;Bradwin,Gary;Liao,KatherineP
• 通讯作者: Liao,KatherineP