Low serum Klotho reflects senile inflammation in middle-aged and elderly patients with coronary atherosclerosis

Coronary atherosclerotic disease (CAD) is one of the leading causes for cardiovascular mortality and is an urgent public health concern owing to high prevalence and poor prognosis [1]. Although atherosclerosis has been shown to be a chronic vascular disease driven by multiple risk factors, the understanding on atherogenesis is still rather limited [2]. Moreover, even though optimal therapy strategies including guideline-directed medication and revascularization have been conducted, high residual risk remains to be reduced [3]. Currently, atherosclerosis is also regarded as a phenotype of vascular aging characterized by lipid deposition and chronic inflammation [4]. Based on the effect of aging and inflammation in CAD, novel relevant biomarkers and therapeutic targets are increasingly required to be explored upon current challenge.

Klotho is an important endogenous pleiotropic protein, which is mainly expressed in renal proximal tubule and secreted into the blood [5]. Decreased circulating Klotho is considered to reflect renal impairment and premature aging, and have been found to be a therapeutic target against accelerated aging [5]. Previous studies exhibited the correlation between Klotho level and coronary/carotid atherosclerosis [6], [7]. However, the relationship between Klotho and inflammatory indicators remains unclear in coronary atherosclerosis. Notably, in recent studies, anti-inflammatory therapy of canakinumab targeting interleukin-1β led to a significant reduction of recurrent cardiovascular events; anti-inflammatory effect of colchicine reduced cardiovascular risk in patients with chronic coronary disease as well; yet methotrexate failed to improve inflammatory parameters and cardiovascular outcomes [8], [9], [10]. These results suggested that atherosclerotic disease had its specific inflammatory manifestation, including characteristic inflammatory cells, cytokines and related signal pathways, and only precisely targeting inflammatory response could help to control cardiovascular risk [11]. Importantly, senile inflammation has been considered as an important driving factor for progression of atherosclerosis [12]. Hence, the impact of aging-related cytokines on inflammatory diseases should be underlined in middle-aged and elderly population, which contributes to risk prediction.

In view of this, we conducted this observational study to investigate the correlation of serum Klotho with inflammatory parameters, and attempted to provide related clues and references for future exploration.

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