We read with great interest the article entitled ‘High levels of cystatin C predict the metabolic syndrome: the prospective Malmö Diet and Cancer Study’ by Magnusson et al. . The authors aimed to investigate whether plasma levels of serum cystatin-C (s-CC) predict new-onset metabolic syndrome (MetS) as well as long-term progression and incidence of the different components of the MetS. They concluded that s-CC may adversely affect metabolic factors, particularly abdominal obesity, thus contributing to the development of MetS. They also suggested that the results of their study may help to explain the link between s-CC and development of cardiovascular disease (CVD). The study was well designed and presented, and the authors have made an important contribution to the literature in this field.
Serum cystatin-C is a sensitive indicator of glomerular filtration rate (GFR) and renal dysfunction  and has also been demonstrated to be a predictive marker of CVD. However, the cause of this relationship is not yet clear. Chronic kidney disease (CKD) can be recognized as a surrogate marker for CVD risk. This means that if patients have either an elevated serum creatinine concentration or a raised level of s-CC (a novel marker of GFR), they have a high risk of experiencing any cardiovascular event in future. There may be an indirect relationship between s-CC levels and CVD risk through renal dysfunction and its effect on endothelial function and inflammation, so that a close direct association cannot be shown. Higher s-CC concentrations were also associated with higher vascular and nonvascular mortality rates throughout the range studied, and these associations were independent of age, prior disease and known vascular risk factors . On the other hand, GFR as measured by s-CC is an important determinant of plasma homocysteine (Hcy) and serum methylmalonic acid (MMA) levels in the elderly. The prevalence of elevated Hcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for the evaluation of Hcy and MMA concentrations in relation to both s-CC and serum creatinine have been presented . Additionally, s-CC may not accurately reflect kidney function in patients with primary and secondary (central) thyroid dysfunction, because levels may be affected by thyroid dysfunction . For this reason, information regarding vitamin B12, thyroid status and folate levels may have been useful in the present study.
The MetS is a clinical entity comprising risk factors for CVD such as hypertension, glucose intolerance, atherogenic lipid profile, abdominal obesity, lack of physical activity and an increased inflammatory state. A number of recent studies have demonstrated a correlation between inflammatory mediators and components of the MetS , and an association between inflammatory markers and the severity of the MetS has also been reported . These indicators of inflammation in the MetS may be the early markers of the development of CVD. Although in the present study, the authors have shown that patients with the MetS had significantly higher levels of inflammatory mediators compared with those without, they did not investigate inflammatory mediator status according to the severity of MetS . Evaluation of the association between the severity of MetS and s-CC levels would have provided important additional information.
Elevation of inflammatory mediators is a common sign of atherosclerotic involvement of the vascular structure, indicating the presence of coronary artery disease, cerebrovascular disease, peripheral arterial disease or chronic inflammatory disease . Inflammation can also be affected by atherosclerotic risk factors such as alcohol consumption and hypothyroidism. Thus, it is noteworthy that alcohol consumption, insulin resistance, hypothyroidism, heart failure, cerebrovascular disease, peripheral arterial disease and chronic inflammatory disease were not assessed in this study . Consideration of these factors would have been useful. In addition, some medications such as antihypertensive treatment (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and beta blockers), statins, medication for weight loss, and a medical history of drug addiction may influence the levels of inflammatory mediators. Evaluation of such medications would also have been useful and indeed may have affected the results.
The presence of the MetS may be associated with many variables including socio-economic and lifestyle factors. Individuals with a low level of education and low socio-economic status have been shown to be at a higher risk of the MetS. Such individuals are usually characterized by poor dietary habits, low levels of physical activity and a high rate of potentially harmful behaviours, all of which increase the risk of metabolic abnormalities . Evaluation of these factors in the present study may have increased the validity of the results.
Finally, s-CC has been used as a measure of inflammatory status, but it can be affected by many factors. Therefore, s-CC alone without other inflammatory markers may not provide clinicians with sufficient information about the MetS. For this reason, we propose that s-CC levels should be evaluated together with other serum inflammatory markers in routine clinical practice . We believe that the findings of this study will provide a guide for further studies of s-CC as a surrogate marker of endothelial dysfunction in patients with the MetS.