Abstract
Background
Klotho, which was originally identified as an aging suppressor, is a key regulator of bone and mineral metabolism. Transmembrane and soluble forms of Klotho protein have been identified. The transmembrane form serves as an obligate co-receptor for fibroblast growth factor 23 (FGF23). However, the physiological importance of soluble form of Klotho has not been determined.
Purpose
The present study aimed to test the hypothesis that circulating soluble Klotho levels can predict the presence or extent of coronary artery calcification (CAC) in patients with coronary artery disease.
Methods
We analyzed CAC of culprit lesions in patients with 75 stable angina pectoris who were not on dialysis and were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). Arc and length of each calcium within the culprit lesion was measured by IVUS. The main outcome measure was the calcium index; a volumetric IVUS-derived measure which was calculated as total calcium length/lesion length × maximal calcium arc/360°. Low calcium index was defined as calcium index <0.042 of the first quartile value. Serum Klotho and FGF23 were measured before PCI. Patients were divided into two groups according to median serum Klotho value: low-Klotho (n=37, ≤460 pg/mL) and high-Klotho group (n=38, >460 pg/mL).
Results
Compared with patients with low-Klotho, those with high-Klotho had higher estimated glomerular filtration rate (eGFR) (69±20 vs. 55±16 mL/min/1.73 m2, p<0.001), lower FGF23 levels (51±24 vs. 67±41 pg/mL, p=0.010). Patients with high-Klotho had significantly lower calcium index than those with low-Klotho (0.17±0.21 vs. 0.24±0.23, p=0.043). Serum Klotho levels correlated significantly and inversely with calcium index (r=−0.31, p=0.006). The correlation between Klotho and calcium index was pronounced at analysis in patients with eGFR <60 mL/min/1.73 m2 (r=−0.52, p<0.001). Logistic regression analysis showed that high-Klotho is a sole significant independent factor associated with low calcium index (odds ratio 7.17, p=0.004). Presence of high-Klotho had high sensitivity and negative predictive value for identifying low calcium index (83% and 92%, respectively).
Conclusions
Serum Klotho values were independently and inversely associated with the degree of CAC assessed by IVUS. These findings have important clinical implications for serum Klotho as a biomarker that reflects the extent of CAC.
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