Cardiovascular Disease in Inflammatory Joint Disorders:The interplay between risk factors, inflammation and therapy

Scope of this thesis In this thesis the cardiovascular disease (CVD) risk in inflammatory joint diseases (IJD) was investigated, focusing on rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We aimed to create awareness of this high CVD risk by investigating the magnitude of CVD prevalence in IJD patients over the last decades, also considering new treatment modalities such as biological disease modifying antirheumatic drugs (bDMARD) and imaging techniques such as 18-fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT). In addition, traditional and novel risk factors for CVD and the effects of anti-inflammatory therapy on these risk factors were assessed. Lastly, we revised new EULAR recommendations for CVD risk management in IJD and proposed ideas for future research. Conclusion Atherosclerosis is an inflammatory process, which is further enhanced by the chronic inflammation inherent to IJD. This has implications for health care professionals, especially rheumatologists and cardiologists, but IJD patients should also be aware of their increased CVD risk and take timely precautions. Acknowledging this high risk is an important step preceding the implementation of strategies for prediction, prevention and management of CVD in IJD. There lies an evidence gap which needs to be filled in the future and general practice guidelines need to be developed to reduce CVD risk in these patients

Cardiovascular Disease in Inflammatory Joint Disorders: The interplay between risk factors, inflammation and therapy

Scope of this thesis In this thesis the cardiovascular disease (CVD) risk in inflammatory joint diseases (IJD) was investigated, focusing on rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We aimed to create awareness of this high CVD risk by investigating the magnitude of CVD prevalence in IJD patients over the last decades, also considering new treatment modalities such as biological disease modifying antirheumatic drugs (bDMARD) and imaging techniques such as 18-fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT). In addition, traditional and novel risk factors for CVD and the effects of anti-inflammatory therapy on these risk factors were assessed. Lastly, we revised new EULAR recommendations for CVD risk management in IJD and proposed ideas for future research. Conclusion Atherosclerosis is an inflammatory process, which is further enhanced by the chronic inflammation inherent to IJD. This has implications for health care professionals, especially rheumatologists and cardiologists, but IJD patients should also be aware of their increased CVD risk and take timely precautions. Acknowledging this high risk is an important step preceding the implementation of strategies for prediction, prevention and management of CVD in IJD. There lies an evidence gap which needs to be filled in the future and general practice guidelines need to be developed to reduce CVD risk in these patients

Cardiovascular Disease in Inflammatory Joint Disorders: The interplay between risk factors, inflammation and therapy

Scope of this thesis In this thesis the cardiovascular disease (CVD) risk in inflammatory joint diseases (IJD) was investigated, focusing on rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We aimed to create awareness of this high CVD risk by investigating the magnitude of CVD prevalence in IJD patients over the last decades, also considering new treatment modalities such as biological disease modifying antirheumatic drugs (bDMARD) and imaging techniques such as 18-fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT). In addition, traditional and novel risk factors for CVD and the effects of anti-inflammatory therapy on these risk factors were assessed. Lastly, we revised new EULAR recommendations for CVD risk management in IJD and proposed ideas for future research. Conclusion Atherosclerosis is an inflammatory process, which is further enhanced by the chronic inflammation inherent to IJD. This has implications for health care professionals, especially rheumatologists and cardiologists, but IJD patients should also be aware of their increased CVD risk and take timely precautions. Acknowledging this high risk is an important step preceding the implementation of strategies for prediction, prevention and management of CVD in IJD. There lies an evidence gap which needs to be filled in the future and general practice guidelines need to be developed to reduce CVD risk in these patients

The effects of 5-year etanercept therapy on cardiovascular risk factors in patients with psoriatic arthritis

Objective. To investigate the effects of etanercept (ETN) on lipid metabolism and other known cardiovascular disease (CVD) risk factors in patients with psoriatic arthritis (PsA). Methods. In an observational cohort of 118 consecutive patients with PsA, CVD risk factors were assessed over 5 years. Mixed-model analyses were performed to investigate the effects of ETN therapy on CVD risk factors over time. Results. Disease Activity Score in 28 joints, C-reactive protein (CRP), and erythrocyte sedimentation rate decreased during therapy with ETN. There was an increase in total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), and low-density lipoprotein cholesterol. The TC/HDLc ratio remained unaltered. The apolipoprotein B to apolipoprotein A-I (apoB/apoA-I) ratio decreased significantly. An increase in CRP was associated with an increase in the apoB/apoA-1 ratio. Conclusion. Serum lipid concentrations showed small changes over a 5-year period of ETN therapy and were inversely associated with inflammatory markers. Other CVD risk factors remained stable. The apoB/apoA-1 ratio decreased over time and an increase in disease activity was associated with an increase in this ratio. However, this modest lipid modulation cannot explain the observed beneficial CV effects of ETN, and ETN likely exerts those effects through inflammation-related mechanisms

Effect of anti-inflammatory therapy on vascular biomarkers for subclinical cardiovascular disease in rheumatoid arthritis patients

OBJECTIVE: To assess the effect of 4 years of anti-inflammatory therapy on markers of subclinical vascular disease in rheumatoid arthritis patients. METHODS: Carotid intima media thickness (IMT), augmentation index (AIx@75) and pulse wave velocity (PWV) measurements were performed repeatedly in 61 RA patients (30 early RA starting with csDMARDs and 31 established RA starting with adalimumab) for 4 years. These markers were also measured in 29 controls with osteoarthritis at baseline (BL). RESULTS: IMT and AIx@75 at BL were higher in RA compared to OA, while PWV was higher in OA. In RA patients, AIx@75 and PWV decreased in the first 6 months after starting anti-inflammatory therapy. At 48 M, the level of AIx@75 remained lower than before therapy, while PWV at 48 M was comparable to BL (AIx@75: BL 28% (95% confidence interval 25-30%), 6 M 23% (20-26%), 48 M 25% (22-28%); PWV: BL 8.5 (7.8-9.2), 6 M 8.0 (7.1-8.9), 48 M 8.6 (7.6-9.6) m/s). IMT remained stable. There was an effect of disease activity (longitudinally, adjusted for changes over time) on IMT, AIx@75 and PWV. CONCLUSION: This study suggests modest beneficial changes in some surrogate markers of subclinical vascular disease after anti-inflammatory therapy. These changes were associated with improvement in disease activity markers. Whether or not these beneficial changes ultimately predict a reduction in clinicalcardiovascular endpoints remains to be established in prospective studies

Interferon regulatory factor 5 gene variants rs2004640 and rs4728142 are associated with carotid intima media thickness but not with cardiovascular events in rheumatoid arthritis

OBJECTIVES: Rheumatoid arthritis (RA) is associated with cardiovascular (CV) morbidity and mortality. Interferon regulatory factor 5 (IRF5) gene polymorphisms rs2004640 and rs4728142 have been associated with autoimmune diseases, but also with atherosclerosis. Differences in IRF5 gene expression can lead to the production of different interferons and might play a role in the atherogenic process in RA. METHODS: We investigated the effects of IRF5 gene variants rs2004640 and rs4728142 on clinical parameters related to atherosclerosis, such as cIMT (in subgroup n=101), and new CV events (in whole cohort n=353). RESULTS: For rs2004640, cIMT values at baseline were highest within the group of patients carrying the GG-genotype, followed by GT- and TT- genotypes, which was statistically significant. Over time patients with the TT-genotype had the highest increase in cIMT. For rs4728142 cIMT values were also the highest for patients with the GG-genotype at baseline, but the difference between the groups was not statistically significant. Over time the highest increase in cIMT was in the patients with the AA-genotype. Both rs2004640 and rs4728142 were not associated with new CV events during follow-up. CONCLUSIONS: IRF5 alleles are associated with changes in cIMT, but not with new CV events in RA. Although these findings implicate a role of the IRF5 transcription pathway in atherosclerosis, IRF5 single nucleotide polymorphisms do not appear to increase the risk of future CV events