Does Aggressive Treatment in Early RA Reduce Biomarkers of Cardiovascular Risk?
早期 RA 的积极治疗是否会降低心血管风险的生物标志物?
基本信息
- 批准号:8099670
- 负责人:
- 金额:$ 16.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2013-05-31
- 项目状态:已结题
- 来源:
- 关键词:Anti-Inflammatory AgentsAnti-inflammatoryAntirheumatic AgentsArthritisAtherosclerosisBiological MarkersC-reactive proteinCardiovascular DiseasesCardiovascular systemCause of DeathCessation of lifeCholesterolClinical DataClinical ResearchCombined Modality TherapyCoronary heart diseaseDataDetectionDevelopmentDiseaseEarly treatmentEtanerceptEventFunctional disorderGeneral PopulationHeterogeneityHigh Density Lipoprotein CholesterolHigh Density LipoproteinsHydroxychloroquineInflammationInflammatoryLinkLipidsLipoproteinsLow Density Lipoprotein oxidationMaintenanceMethotrexateMorbidity - disease ratePatientsPharmaceutical PreparationsPharmacotherapyPlayPredispositionPrevention strategyProteinsPublic HealthRandomizedRheumatoid ArthritisRiskRisk AssessmentRisk FactorsRisk MarkerRisk ReductionRoleSpecimenSulfasalazineSystemic Lupus ErythematosusTNF geneTimeWomanWorkcardiovascular risk factorcohortdesigndisorder controlfollow-upimprovedinhibitor/antagonistmembermortalitynovelpreventprospectiveprotein structure functionpublic health relevancesystemic autoimmune diseasevascular inflammation
项目摘要
DESCRIPTION (provided by applicant): Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with significantly increased cardiovascular (CV) morbidity and mortality. Systemic inflammation from active RA has been strongly linked to cardiovascular death and subclinical atherosclerosis in RA patients. Traditional CV risk factors contribute to CV risk in RA, but these risk factors alone are not sufficient to explain the magnitude of CV risk associated with RA. Changes in novel risk factors such as the quality as well as quantity of high density lipoprotein (HDL) may be necessary to more fully explain CV risk in RA. Substantial evidence has accumulated that dysfunctional HDL may play a role in the development of atherosclerosis. The presence of abnormal, pro-inflammatory HDL (piHDL) is associated with coronary heart disease (CHD) in the general population and is more prevalent in patients with RA. Our preliminary data in a cross-sectional RA cohort suggests a significant correlation of HDL function with RA disease activity and systemic inflammation. Higher disease activity, ESR, and C-reactive protein were associated with worse HDL function. Large, well designed prospective clinical studies are needed to further evaluate the effects of disease activity as well as disease treatments on HDL function and other biomarkers of CV risk in patients with RA. We propose: 1)To evaluate the effects of disease activity on traditional and novel biomarkers of CV risk in a 755 patient early RA cohort during two years of treatment, 2)To evaluate the effects of methotrexate monotherapy versus methotrexate combination therapies on traditional and novel biomarkers of CV risk. We hypothesize that systemic inflammation from active RA alters both the quantity and protein structure/function of HDL, impairing its capacity to prevent oxidation of LDL, thus enhancing the development of atherosclerosis. We also hypothesize that improvement in disease activity improves both traditional and novel biomarkers of CV risk, and that methotrexate combination therapy may be more effective at improving CV biomarkers by more effectively controlling disease activity. The significance of the proposed work lies in its potential to conclusively define the effects of RA disease activity, treatment, and disease improvement on both traditional and novel biomarkers of atherosclerotic risk in specimens from a large, 755 patient early RA cohort with minimal prior disease modifying anti-rheumatic drug (DMARD) therapy who were randomized to methotrexate monotherapy or methotrexate combination therapy with etanercept or hydroxychloroquine/sulfasalazine and followed for two years. Long term reduction of CV risk biomarkers with aggressive control of disease activity would provide further rationale for aggressive treatment of early RA. However, the inability to improve novel and/or traditional CV risk markers with currently available DMARDS would provide rationale for the addition of early treatment of RA patients with CV therapies such as statins and other novel CV risk reduction drugs currently in development.
PUBLIC HEALTH RELEVANCE: Patients with rheumatoid arthritis (RA) die 3-18 years earlier then members of the general population and cardiovascular (CV) disease is the leading cause of death. This study will evaluate if aggressive arthritis control with current treatments can improve novel and traditional biomarkers of CV risk in early RA patients followed for two years. Improvement in CV risk markers with disease control would provide further rationale for aggressive treatment of early RA patients, while lack of improvement in CV markers would suggest the need for early treatment with CV protective therapies such as statins (cholesterol-lowering medications) and/or other novel CV risk reduction drugs currently in development.
描述(由申请人提供):类风湿性关节炎(RA)是一种全身性自身免疫性疾病,与心血管(CV)发病率和死亡率显着增加相关。活动性 RA 引起的全身炎症与 RA 患者的心血管死亡和亚临床动脉粥样硬化密切相关。传统的心血管风险因素会导致 RA 的心血管风险,但仅这些风险因素不足以解释与 RA 相关的心血管风险的严重程度。为了更全面地解释 RA 的心血管风险,可能需要改变新的风险因素,例如高密度脂蛋白 (HDL) 的质量和数量。 大量证据表明,功能失调的高密度脂蛋白可能在动脉粥样硬化的发展中发挥作用。异常促炎性 HDL (piHDL) 的存在与普通人群中的冠心病 (CHD) 相关,并且在 RA 患者中更为常见。我们在横断面 RA 队列中的初步数据表明 HDL 功能与 RA 疾病活动性和全身炎症存在显着相关性。较高的疾病活动度、ESR 和 C 反应蛋白与较差的 HDL 功能相关。需要进行大型、精心设计的前瞻性临床研究来进一步评估疾病活动以及疾病治疗对 RA 患者 HDL 功能和其他心血管风险生物标志物的影响。 我们建议:1) 在 755 名早期 RA 队列患者的两年治疗期间,评估疾病活动对传统和新型 CV 风险生物标志物的影响,2) 评估甲氨蝶呤单药治疗与甲氨蝶呤联合治疗对传统和新型 CV 风险生物标志物的影响。 我们假设,活动性 RA 引起的全身炎症会改变 HDL 的数量和蛋白质结构/功能,损害其防止 LDL 氧化的能力,从而促进动脉粥样硬化的发展。我们还假设疾病活动性的改善可以改善心血管风险的传统和新型生物标志物,并且甲氨蝶呤联合疗法可能通过更有效地控制疾病活动来更有效地改善心血管生物标志物。 这项工作的意义在于,它有可能最终确定 RA 疾病活动、治疗和疾病改善对动脉粥样硬化风险的传统和新型生物标志物的影响,这些样本来自一个大型的 755 名早期 RA 队列患者,接受了最低限度的既往疾病缓解抗风湿药物 (DMARD) 治疗,这些患者被随机接受甲氨蝶呤单药治疗或甲氨蝶呤与依那西普联合治疗或 羟氯喹/柳氮磺吡啶并随访两年。通过积极控制疾病活动来长期降低心血管风险生物标志物将为早期 RA 的积极治疗提供进一步的理论依据。然而,目前可用的 DMARDS 无法改善新型和/或传统的 CV 风险标志物,这为 RA 患者添加 CV 疗法(如他汀类药物和目前正在开发的其他新型 CV 风险降低药物)进行早期治疗提供了理由。
公共健康相关性:类风湿性关节炎 (RA) 患者比一般人群早死亡 3-18 年,心血管 (CV) 疾病是导致死亡的主要原因。这项研究将评估采用当前治疗方法积极控制关节炎是否可以改善早期 RA 患者随访两年的新型和传统心血管风险生物标志物。通过疾病控制来改善心血管风险标志物将为早期 RA 患者的积极治疗提供进一步的理由,而心血管标志物缺乏改善则表明需要早期使用他汀类药物(降胆固醇药物)和/或其他目前正在开发的新型降低心血管风险的药物等心血管保护性疗法进行治疗。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Christina Charles-Schoeman其他文献
Christina Charles-Schoeman的其他文献
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{{ truncateString('Christina Charles-Schoeman', 18)}}的其他基金
Mechanisms Linking Joint Inflammation and Atherosclerosis in Rheumatoid Arthritis
类风湿关节炎中关节炎症和动脉粥样硬化的联系机制
- 批准号:
8818588 - 财政年份:2014
- 资助金额:
$ 16.88万 - 项目类别:
Mechanisms Linking Joint Inflammation and Atherosclerosis in Rheumatoid Arthritis
类风湿关节炎中关节炎症和动脉粥样硬化的联系机制
- 批准号:
8965517 - 财政年份:2014
- 资助金额:
$ 16.88万 - 项目类别:
Does Aggressive Treatment in Early RA Reduce Biomarkers of Cardiovascular Risk?
早期 RA 的积极治疗是否会降低心血管风险的生物标志物?
- 批准号:
7990461 - 财政年份:2010
- 资助金额:
$ 16.88万 - 项目类别:
HDL Function as a Biomarker for Atherosclerotic Risk in Rheumatoid Arthritis
HDL 作为类风湿性关节炎动脉粥样硬化风险生物标志物的功能
- 批准号:
8076745 - 财政年份:2009
- 资助金额:
$ 16.88万 - 项目类别:
HDL Function as a Biomarker for Atherosclerotic Risk in Rheumatoid Arthritis
HDL 作为类风湿性关节炎动脉粥样硬化风险生物标志物的功能
- 批准号:
7740004 - 财政年份:2009
- 资助金额:
$ 16.88万 - 项目类别:
HDL Function as a Biomarker for Atherosclerotic Risk in Rheumatoid Arthritis
HDL 作为类风湿性关节炎动脉粥样硬化风险生物标志物的功能
- 批准号:
8299538 - 财政年份:2009
- 资助金额:
$ 16.88万 - 项目类别:
HDL Function as a Biomarker for Atherosclerotic Risk in Rheumatoid Arthritis
HDL 作为类风湿性关节炎动脉粥样硬化风险生物标志物的功能
- 批准号:
7922668 - 财政年份:2009
- 资助金额:
$ 16.88万 - 项目类别:
HDL Function as a Biomarker for Atherosclerotic Risk in Rheumatoid Arthritis
HDL 作为类风湿性关节炎动脉粥样硬化风险生物标志物的功能
- 批准号:
8467027 - 财政年份:2009
- 资助金额:
$ 16.88万 - 项目类别:
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