New endocrine biomarkers and cardiovascular disease: is it time for routinely screening?

Abstract

Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, embryonic development, and various endocrine signaling pathways [1]. Interestingly, FGFs are key players in cell and tissue proliferation and differentiation. In humans, 23 members of the FGF family have been identified and, in particular, both FGF21 and FGF23 have systemic effects [2].FGF21 is expressed in numerous tissues and stimulates glucose uptake in adipocytes [2]. Its effect is additive to insulin activity, and animals receiving FGF21 show an increased fat utilization and lipid metabolism [3]. Interestingly, β-klotho is an essential cofactor for FGF21 activity. Serum FGF21 levels are significantly increased in type 2 diabetes mellitus patients, and enhanced levels also associate with liver fat content in liver diseases and with obesity [4].FGF23 is a recently identified molecule involved in the control of phosphate homeostasis and calcitriol metabolism [5]. FGF23 is a circulating 32-kDa peptide secreted by the osteocytes in response to hyperphosphatemia and calcitriol therapy. It has been demonstrated that in healthy subjects, serum FGF23 levels begin to rise 5 to 6 h after high dietary phosphate intake. Moreover, FG23 is constantly elevated in patients with advanced chronic kidney disease (CKD), due to phosphate overload, even if the clinical relevance of high FGF23 in CKD remains largely unknown. Recent studies indicate that high FGF23 levels are associated with the progression of CKD and with higher mortality rates in hemodialysis patients [6]. This is why it is important to understand the potential differences of FGF23 synthesis, secretion, and metabolic properties in normal renal function conditions and in CKD. FGF23 reduces serum phosphate levels (and also calcium levels) through its concerted action on the kidney and parathyroid glands.α-Klotho is a trans-membrane protein that appears to be involved in cardiovascular aging. Reduced production of α-klotho has been observed in CKD patients, and this may be one of the factors underlying the degenerative processes, such as arteriosclerosis, osteoporosis, and skin atrophy. In addition, klotho mutations have been associated with aging and bone loss. Transgenic mice that overexpress klotho live longer than wild-type mice [7].In the present issue of the journal, Fujita et al.[8] investigate the association between FGF21, FGF23, and α-klotho levels and mean platelet volume (MPV) and platelet distribution width (PDW) in 156 patients affected by cardiovascular disease. Interestingly, MPV was significantly associated negatively with log(FGF21) and positively with log(FGF23), even when antithrombotic drug use was consider in the multivariate analysis. On the contrary, α-klotho levels did not correlate with biomarkers of platelet activity.Recent insights into novel roles of bone biomarkers, such as FGF23 and α-klotho, in vascular biology makes this primarily kidney-derived protein a possible candidate to form a link between bone and cardiovascular morbidity and mortalit...