The metabolic syndrome–arterial stiffness relationship in patients with ischaemic stroke: role of inflammation

The metabolic syndrome (MetS) is a highly prevalent complex clinical disorder, characterised by a clustering of high blood pressure (BP) and some metabolic traits, including elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, glucose intolerance (with or without overt diabetes) and abdominal obesity [1]. In the effort to introduce the MetS into clinical practice, several organisations have attempted to formulate working definitions for its diagnosis [1]. Amongst these definitions, the one suggested by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III), recently updated by an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement, is probably the simplest, most practical and most commonly applied [1]. Although the definition and nosological significance of MetS has been the subject of recent debate [2], it is increasingly recognised as an independent predictor of cardiovascular (CV) diseases, even in absence of diabetes [1,3–8]. The relative risk from the MetS for CV morbidity and mortality is approximately twice as high as for those without the syndrome [1,3]. In some, but not all studies, the strength of its association with cerebrovascular disease was stronger than that for coronary events [3,5]. Najarian et al. [4] examined the risk for stroke in 2097 participants from the Framingham Offspring Study, of whom 22% had MetS alone, 5% had type 2 diabetes alone and 5% had both. Follow-up lasted up to 14 years. After adjustments for typical risk factors, the relative risk for stroke during follow-up was 3.28 for individuals with both MetS and diabetes, and 2.10 and 2.47, respectively, for those with MetS alone and diabetes alone. The authors conclude that MetS and type 2 diabetes are independent risk factors for stroke. Furthermore, they concluded that MetS is more prevalent than type 2 diabetes and, therefore, has a greater populationattributable risk [4]. More recently, it has been shown, in 991 elderly Finnish subjects without diabetes, followed-up for 14 years, that the MetS, regardless of the criteria used for its definition, predicted stroke, even after exclusion of subjects with myocardial infarction and independently from traditional risk factors [6]. Several lines of evidence suggest that the enhanced CV risk associated with MetS may be mediated by the increased prevalence in individuals with MetS of subclinical organ damage, such as left ventricular hypertrophy, microalbuminuria, extracranial or intracranial vascular changes, impaired arterial distensibility [7–11]. Amongst these markers of organ damage, large artery distensibility, during the last decade received increased attention [11–16], in parallel with the widespread availability of non-invasive methods for its assessment [13]. Pulse wave velocity (PWV) measurement is one of the simplest methods to evaluate large artery elasticity [13]. The basic principle of PWV assessment is that, the pulse wave runs along with the arterial tree at a speed, which depends upon the elasticity of the wall itself: the stiffer (i.e. less elastic) the wall the higher the velocity of propagation. PWV measured along the aortic and aortoiliac pathway is the most clinically relevant as the aorta and its first branches are responsible for most of the pathophysiological effects of arterial stiffness [13]. In last years, several longitudinal studies directly demonstrated that aortic stiffness, measured through carotid–femoral PWV, is an independent predictor of all-cause and CV mortality, coronary events and stroke [13]. Thus, aortic stiffness is now well accepted as an intermediate end-point for CV events [13]. Even if the role of inflammation as independent risk factor for atherosclerotic CV diseases is still debated [17,18], it is accepted that systemic subclinical low-grade inflammation, as expressed by high circulating levels of inflammatory markers/mediators, is a common denominator of most cardiovascular risk factors, including the MetS [17], and importantly, it is closely related to impaired arterial elastic properties [13,15]. The study of De Silva et al. [19] published in the current issue of the EJN, showing an increased aortic stiffness in subjects with the MetS, reproduced, in a group of Asian patients with a recent ischaemic cerebrovascular event, the results previously obtained in different populations [8,11–13]. This association between aortic stiffness and MetS lost statistical significance after adjustment for serum erythrocyte sedimentation rate. This seems to be the more interesting finding of the paper, suggesting that inflammation may be the main mediator of the link between the MetS and a reduced arterial elasticity [19].