Collateral cardiovascular damage in inflammatory joint diseases:Focus on cardiac dysfunction

This thesis aims to improve knowledge about the role of systemic inflammation in the development of cardiovascular disease and particularly cardiac dysfunction. Furthermore, to elucidate the added value of cardiac screening in this population. In Part I of this thesis including chapters 2-5, we focus on the role of inflammation in the development of CVD in IJD patients. Chapter 2 describes the prevalence, pathophysiology, and guidelines for CVD in IJD, i.e. RA and gout. In chapter 3 we reviewed the current literature on the effect of anti-inflammatory treatment, i.e. anti-TNF, on the cardiac function and the prevalence and incidence of CHF in RA. We performed echocardiography to assess the effect of anti-TNF on the cardiac function in RA patients with active disease in chapter 4. Part I finishes with chapter 5 describing a case report of a SLE patient with SLE induced heart failure with preserved ejection fraction (HFpEF) where the heart failure was treated with anti-inflammatory therapy. In part II, we focus on the role of systemic inflammation and cardiac diseases in AS patients. In this light, in chapter 6, we performed a large cross-sectional study in AS patients and osteoarthritis (OA) controls, the CARDAS study, to assess the prevalence of cardiac valve disease, conduction disturbances and cardiac dysfunction in AS. In our aim to identify a subgroup of AS patients at risk for aortic valve disease, in chapter 7, we performed a sub study of the CARDAS study to assess the association between HLAB27 genotype and aortic root dilatation and aortic valve regurgitation. Finally, part III reports on clinical trials focusing on relation between systemic inflammation and cardiovascular disease beyond the heart. In chapter 8, we conducted a cross-sectional controlled study in AS patients and healthy controls to assess the difference in retinal vasculature and to assess the value of retinal screening for cardiovascular disease. Furthermore, we assessed the effect of anti-inflammatory therapy on insulin resistance and body composition in RA patients in chapter 9

The effect of biological DMARDs on the risk of congestive heart failure in rheumatoid arthritis: a systematic review

Introduction: A common cardiovascular manifestation in rheumatoid arthritis (RA) is congestive heart failure (CHF) in which inflammation is considered to play a pivotal role. Although anti-inflammatory therapy such as biological disease-modifying anti-rheumatic drugs (bDMARDs) have the potential of improving the cardiac function and reducing the risk of CHF, the published studies showed contrasting results. This review aims to systematically summarize and analyze literature regarding the effect of bDMARDs on the cardiac function and on the risk of CHF in RA. Areas covered: Observational cohort, randomized controlled trials and case-controlled studies were included. The systematic literature search was conducted in PubMed, Wiley/Embase, Cochrane, Web of Science and clinicaltrials.gov (up to 2017). Two authors assessed abstracts for inclusion and methodological quality was assessed by one reviewer. Expert opinion: RA patients have a clinically relevant increased risk of developing CHF needing further attention. However, we found a lack of high quality studies. Future studies should focus on distinguishing the effect of myocardial inflammation reduction versus antibody-specific myocardial cellular effects of bDMARDs to improve the understanding of the effects of bDMARDs in RA patients and the relation with the development of CHF

Clinical improvement of cardiac function in a patient with systemic lupus erythematosus and heart failure with preserved ejection fraction treated with belimumab

We present a 51-year-old Caucasian woman, with a medical history of systemic lupus erythematosus (SLE) who had dyspnoea at exertion. The SLE was clinically quiescent but serologically active. Echocardiography showed preserved left ventricular (LV) systolic function, pseudonormal mitral inflow pattern (diastolic dysfunction grade III), absence of wall motion abnormalities and elevated E/e' at exercise. An exercise right heart catheterisation was performed, confirming the diagnosis of heart failure with preserved ejection fraction (HFpEF). In the absence of other possible causes, we assumed that HFpEF was mediated by systemic inflammation secondary to SLE. Based on the Paulus' paradigm, that systemic inflammation may lead to diastolic dysfunction, we decided to add belimumab (a biological agent against soluble B-lymphocyte stimulator protein). After 16 weeks of treatment, patient reported an improved condition. Also, cardiopulmonary exercise test and echocardiography results improved, confirming resolution of the underlying LV diastolic dysfunction. This case supports the idea that targeting inflammation has therapeutic potential in a subset of HFpEF-patients

Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout

The increased risk of cardiovascular morbidity and mortality in rheumatoid arthritis and gout has been increasingly acknowledged in past decades, with accumulating evidence that gout, just as with rheumatoid arthritis, is an independent cardiovascular risk factor. Although both diseases have a completely different pathogenesis, the underlying pathophysiological mechanisms in systemic inflammation overlap to some extent. Following the recognition that systemic inflammation has an important causative role in cardiovascular disease, anti-inflammatory therapy in both conditions and urate-lowering therapies in gout are expected to lower the cardiovascular burden of patients. Unfortunately, much of the existing data showing that urate-lowering therapy has consistent beneficial effects on cardiovascular outcomes in patients with gout are of low quality and contradictory. We will discuss the latest evidence in this respect. Cardiovascular disease risk management for patients with rheumatoid arthritis and gout is essential. Clinical guidelines and implementation of cardiovascular risk management in daily clinical practice, as well as unmet needs and areas for further investigation, will be discussed

The effect of anti-tnf therapy on cardiac function in rheumatoid arthritis: An observational study

Congestive heart failure (CHF) is the second most prevalent cause of death in rheumatoid arthritis (RA). The systemic inflammatory state in RA patients is deemed responsible for this finding. Anti-inflammatory treatment with anti-tumor necrosis factor (anti-TNF) therapy decreases CV risk and subsequently might improve the cardiac function by lowering the overall inflammatory state. This study investigated the effect of anti-TNF on the cardiac function in RA patients. Fifty one RA patients were included, of which thirty three completed follow-up. Included patients were >18 years, had moderate–high disease activity and no history of cardiac disease. Patients were assessed at baseline and after six months of anti-TNF treatment. Patients underwent conventional Speckle tracking and tissue Doppler echocardiography in combination with clinical and laboratory assessments at baseline and follow-up. The left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) showed no changes during follow-up, LVEF 63% (±9) to 62% (±8) p = 0.097 and GLS −20 (±4) to −20 (±3) p = 0.79, respectively. Furthermore, E/e’ nor E/A changed significantly between baseline and follow-up, respectively 8 (7–9) and 8 (7–9) p = 0.17 and 1.1 (±0.4) and 1.1 (±0.4) p = 0.94. Follow-up NT-proBNP decreased with 23%, from 89 ng/L (47–142) to 69 ng/L (42–155), p = 0.10. Regression analysis revealed no association between change in inflammatory variables and cardiac function. Echocardiography showed no effect of anti-TNF treatment on the cardiac function in RA patients with low prevalence of cardiac dysfunction. Moreover, NT-proBNP decreased, possibly indicating (subtle) improvement of the cardiac function

The Prevalence of Cardiac Diseases in a Contemporary Large Cohort of Dutch Elderly Ankylosing Spondylitis Patients—The CARDAS Study

Objectives: The aim of the present study was to determine the prevalence of specific cardiac manifestations, i.e., conduction disorders, valvular disease and diastolic left ventricular (LV) dysfunction, in a large cross-sectional controlled cohort of elderly ankylosing spondylitis (AS) patients. Methods: This cross-sectional study assessed the prevalence of valvular disease, conduction disorders and LV dysfunction in 193 randomly selected AS patients compared with 74 osteoarthritis (OA) controls aged 50–75 years. Patients underwent conventional and tissue Doppler echocardiography in combination with clinical and laboratory assessments. Multivariate regression analyses were performed to compare the odds of mitral valve regurgitation (MVR) and aortic valve regurgitation (AVR) between AS patients and OA controls. Results: The prevalence of diastolic dysfunction was trivial and comparable in AS patients compared to controls (respectively, 4% and 3%) and had no further clinical relevance. In addition, the prevalence of conduction disturbances was similar in both groups, with little clinical relevance, respectively 23% vs. 24%. The prevalence of AVR was significantly higher in AS patients compared to the controls, respectively 23% (9% trace, 12% mild, 1% moderate, 1% severe, 1% prosthesis) vs. 11%, p = 0.04. After correcting for age, sex and CV risk factors, AS patients had an odds ratio of 4.5 (95% CI 1.1–13.6) for AVR compared to the controls. In contrast, the prevalence values of MVR were similar and mostly not clinically relevant in AS patients and controls, respectively 36% and 32% and p = 0.46. Conclusion: The prevalence of diastolic LV dysfunction and conduction disorders was mostly not clinically relevant, and similar in AS patients and controls. However, AS patients had an up to five times increased odds to develop AVR compared to controls. Therefore, echocardiographic screening of elderly (50–75 years) AS patients should be considered