All the research in this thesis is based on the Franciscus Rheumatoid Arthritis aNd Cardiovascular Intervention Study (FRANCIS), an open label randomized clinical trial. The main focus of this thesis is on the role of traditional CVD risk factors on CVD in RA; their prevalence, their association with subclinical atherosclerosis and whether a tight treatment protocol on CVD risk factors results in improved treatment of traditional CVD risk factors. We investigated the prevalence of traditional CVD risk factors in the FRANCIS population, using the SCORE model and two suggested modified SCORE models by the European league against rheumatism (EULAR) and the Dutch guideline for CVD risk management.
We found that hypertension and hyperlipidemia in RA patients are underdiagnosed and undertreated. In the general population, the cornerstone of CVD risk reduction is lifestyle recommendations like following a healthy diet, cessation of smoking and performing daily exercise. We know that patients adherence to lifestyle recommendations and drug therapy for preventive measures is generally low. We investigated adherence to cardiovascular interventions (prescribed drugs and lifestyle) in FRANCIS patients by using a questionnaire. The self/reported adherence to doctors advices in general was high, however, when more detailed questions about specific lifestyle interventions were asked adherence rates were considerably lower.
A commonly used measurement for the detection of subclinical atherosclerosis is the measurement of the carotid intima media thickness (cIMT). A recent meta-analysis by Wang et al. showed that the cIMT is increased in RA compared to healthy controls. Furthermore, in RA there is an increased progression rate of cIMT described compared to controls (10). We investigated the association of several traditional and RA-specific CVD risk factors with cIMT and compared these results with healthy controls. We found no correlation between RA specific risk factors such as anti-CCP, RF and disease activity (DAS28) and cIMT.
Since traditional and RA-specific CVD risk factors cannot fully explain the excess CVD risk in RA search for novel CVD risk factors in RA is warranted. We therefore investigated apolipoprotein B48 levels, the structural protein of chylomicrons and a marker of postprandial lipemia, in RA patients. Postprandial lipemia is of exceptional interest since it is linked to both inflammation and the traditional risk factor hyperlipidemia. We found high apoB48 levels in RA patients. These levels are higher them previously found levels in other CVD risk category patients such as patients with diabetes or hyperlipidemia.
Besides searching for new and RA specific CVD risk factors it is important to investigate the effect of treatment of traditional CVD risk factors. We investigated the effect of a tight treatment protocal vs usual care regarding traditional CVD risk factors in RA after two years of follow-up, which is an interim analysis of the original study. The usual care group were less likely to be adequately treated for their CVD risk factors. No difference in cIMT was found between the two groups after 2 years of follow up.

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Financial support for the FRANCIS is generously provided by the board of directors of the Franciscus Gasthuis, the Foundation for Research of the Department of Internal Medicine, Franciscus Gasthuis, and the Coolsingel Foundation, Rotterdam
J.M.W. Hazes (Mieke) , M. Castro Cabezas (Manuel) , D. van Zeben (Derkjen)
Erasmus University Rotterdam

Van Breukelen-van der Stoep, D. (2017, November 21). Cardiovascular Risk in Rheumatoid Arthritis Patients, Diagnosis and Treatment: a report of the FRANCIS. Retrieved from