Abstract
BackgroundFerritin, a crucial element for iron homeostasis, is associated with chronic diseases characterized by subclinical inflammation such as essential arterial hypertension and type 2 diabetes mellitus (T2DM), showing a prognostic value in different clinical settings. We investigated whether ferritin is associated with arterial stiffness (AS), an early indicator of atherosclerosis, and if it could act as effect modifier on the relationship between inflammation and AS in hypertensive patients with different glucose tolerance.MethodsWe enrolled 462 newly diagnosed untreated hypertensive (HT) patients. All subjects underwent an oral glucose tolerance test. Insulin sensitivity was assessed by MATSUDA index and ferritin levels were estimated by immunoradiometric assay. AS was defined by carotid-femoral pulse wave velocity (PWV).ResultsOut of 462 patients, 271 showed normal glucose tolerance (HT/NGT), 146 impaired glucose tolerance (HT/IGT) and 45 were diabetic (HT/T2DM). Iron levels significantly decreased and transferrin and ferritin significantly increased from the first to the third group. PWV values were significantly higher in HT/IGT and HT/T2DM patients. PWV was related directly with ferritin, high sensitivity C reactive protein (hs-CRP), transferrin, and inversely with MATSUDA index. Ferritin resulted the strongest determinant of PWV explaining a 14.9% of its variation; moreover it was a strong modifier of the relationship between hs-CRP and PWV. The estimated augmentation in PWV portended by a fixed increase in hs-CRP, was higher across increasing values of ferritin.ConclusionFerritin represents an independent risk factor of arterial stiffness in our study population and a strong effect modifier on the relationship between inflammation and PWV. However, further studies are needed to fully elucidate the potential role of this biomarker in human atherosclerosis.
Highlights
Ferritin, a crucial element for iron homeostasis, is associated with chronic diseases characterized by subclinical inflammation such as essential arterial hypertension and type 2 diabetes mellitus (T2DM), showing a prognostic value in different clinical settings
In a large group of naïve hypertensive patients with different glucose tolerance status, we addressed the following hypotheses: (1) to assess the relationships between ferritin levels in the normal range with pulse wave velocity (PWV) and glucose tolerance and to evaluate whether such associations are paralleled by a concomitant increase in high-sensitivity C reactive protein (hs-CRP); (2) to test whether circulating levels of ferritin are related to PWV independently of insulin sensitivity MATSUDA index and other potential confounders; (3) to verify whether inflammation acts as an effect modifier of the link between ferritin and PWV
Study population Out of 462 hypertensive (HT) patients examined by oral glucose tolerance test (OGTT), 271 (58.7%) showed normal glucose tolerance (HT/Normal glucose tolerance (NGT)), 146 (31.6%) impaired glucose tolerance (HT/ IGT) and 45 (9.7%) type 2 diabetes mellitus (HT/T2DM)
Summary
A crucial element for iron homeostasis, is associated with chronic diseases characterized by subclinical inflammation such as essential arterial hypertension and type 2 diabetes mellitus (T2DM), showing a prognostic value in different clinical settings. Several studies report a direct association between serum ferritin levels and chronic inflammation of mild degree [7,8,9,10,11]. Serum ferritin levels resulted to be directly related to insulin-resistance and incident risk of type 2 diabetes mellitus (T2DM), independently of traditional risk factors [7, 8], especially when high-sensitivity C reactive protein (hs-CRP) is increased [9]. In various populations it has been demonstrated that ferritin is associated with a high risk of arterial hypertension development [10, 11], this latter being the most common risk factor of cardiovascular (CV) events and disability as well [12]
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