Reduced Klotho is associated with the presence and severity of coronary artery disease

Objective Klotho is involved in vascular health. We aimed to analyse in a cross-sectional study the relationship between Klotho and human coronary artery disease (CAD). Methods The study included 371 subjects who underwent coronary angiography and 70 patients who underwent elective cardiac surgery recruited between May 2008 and June 2009. The presence and severity (stenosis index) of CAD, cardiovascular risk factors, Klotho gene expression in the thoracic aorta, and serum soluble Klotho concentrations were evaluated. Results The soluble Klotho concentration was lower (p<0.001) in patients with significant CAD (n=233). The maximal stenosis observed in every epicardial artery and the stenosis severity index was significantly lower in patients within the higher soluble Klotho concentrations (p<0.0001). Multiple regression analysis showed that serum Klotho concentrations were inverse and significantly associated with CAD (adjusted R-2=0.67, p<0.001). Multivariate logistic regression analysis showed that risk factors for significant CAD included age, diabetes, smoking and inflammation, whereas high serum Klotho values were associated with a lower risk for CAD. Lower mRNA expression level of Klotho was observed in 46 patients with significant CAD, as compared with subjects without CAD (p=0.01). Logistic regression analysis showed that high Klotho gene expression was independently associated with lower risk for CAD. Conclusions Patients with significant CAD present lower soluble concentrations of Klotho, as well as reduced levels of Klotho gene expression in the vascular wall. Reduced serum Klotho concentrations and decreased vascular Klotho gene expression were associated with the presence and severity of CAD independently of established cardiovascular risk factors.