The same was carried out when cIMT was explained separately for the left and the right carotid artery. searched for content articles comparing endothelial dysfunction (flow-mediated dilation, nitroglycerin-mediated dilation and peripheral arterial tonometry), vascular tightness (tightness index, pulse wave velocity) and carotid intima-media thickness (cIMT) between individuals and settings. Two investigators assessed the content articles for eligibility and evaluated quality. Results Thirty studies were included. For those results, moderate to high heterogeneity between studies was found. Most studies reported a decreased flow-mediated dilation in the whole KD- and CAA-positive group compared to settings, while data on CAA-negative individuals were conflicting. The tightness index was improved in the majority of studies evaluating the whole KD- and CAA-positive group, but not in most studies on CAA-negative individuals. Mean cIMT was neither significantly increased in the whole KD-group nor in the CAA-positive group nor in most studies studying CAA-negative individuals. Studies measuring maximum cIMT were conflicting. Conclusion Literature suggests that surrogate markers for CVD risk in KD individuals are improved in CAA-positive but not in CAA-negative individuals. This may indicate that CAA-positive individuals should be monitored for CVD in later on life. The results of this review have to be interpreted with care due to considerable heterogeneity between studies and methodological limitations, as well as the lack of long-term follow-up studies. Intro Kawasaki disease (KD) is definitely a pediatric vasculitis primarily affecting children under the age of 5. Coronary artery aneurysms (CAA) develop in 25% of untreated and 5C15% of individuals treated with intravenous immunoglobulins, making it the most common cause of pediatric acquired heart disease in the Western world. It can be hypothesized that, due to the earlier systemic vasculitis, individuals with KD have an increased risk for cardiovascular disease (CVD) at a later on age, apart from the presence or absence of CAA. This hypothesis is definitely difficult to test since KD was first described less than 50 years ago and therefore most of the KD individuals are too young to have experienced cardiovascular events. In recent years, several non-invasive surrogate markers of CVD risk have become available. Endothelial dysfunction can be measured FLT3-IN-1 by flow-mediated dilatation (FMD), nitroglycerin-mediated dilation (NMD) or peripheral arterial tonometry (PAT) [2,3]. Peripheral arterial tightness can also be an indication of improved CVD risk. It can be measured by pulse wave velocity (PWV) or FLT3-IN-1 from the beta tightness index (SI) . FLT3-IN-1 Furthermore, structural changes in the arterial wall can be found by measuring the carotid intima-media thickness (cIMT), well-established surrogate marker of atherosclerosis and subsequent predictor of cardiovascular events [5,6]. The aim of this study was to systematically review and meta-analyze the existing literature concerning CVD risk after KD, as measured by surrogate markers. Methods Search strategies We carried out a systematic literature search of Medline (1966-September 2014) and Embase (1980-September 2014) for studies dealing with KD and surrogate markers of cardiovascular risk (i.e. endothelial dysfunction, peripheral arterial tightness and cIMT). We used two domains of MeSH terms and free text words combined by AND, and in each website the terms were combined by OR. The 1st domain contained terms of KD (including all synonyms and abbreviations), and the second contained terms of surrogate markers of cardiovascular risk (including FLT3-IN-1 all synonyms, abbreviations and free word text such as carotid intima-media thickness, vascular tightness, endothelial dysfunction, flow-mediated dilatation, pulse wave velocity, peripheral arterial tonometry). The complete protocol is authorized in the Prospero database under CRD42014005706, the PRISMA checklist and Medline electronic search strategy are added as S1 PRISMA Checklist and S1 File. Study selection and quality assessment We selected those original studies that reported on surrogate markers of cardiovascular risk (i.e. endothelial dysfunction [FMD, NMD, PAT], vascular tightness [PWV, SI] and cIMT) in KD individuals. Studies were excluded if healthy control groups were not available within the same studies, if lipid-lowering medication was used when measuring subjects, or if data contained preliminary results. Furthermore, because IFI16 of the possible influence of the acute inflammation, studies measuring individuals within 6 months after the acute phase were excluded. Language restrictions were not imposed. The selection process was divided into three successive phases: title-, abstract- and manuscript selection. Two investigators (SD and CT) individually determined eligibility of the retrieved studies, relating to predefined criteria. Using an modified version of the Newcastle-Ottawa level for observational studies (S1 Table: Quality assessment criteria), the same investigators.