Is Low Serum Klotho Level Associated with Alterations in Coronary Flow Reserve?

BACKGROUND: The Klotho gene, described as an "aging suppressor" gene, encodes a single-pass transmembrane protein. The extracellular part of Klotho is cleaved and released into the circulation where it may function as a vasculoprotective hormone. Coronary flow reserve (CFR) is accepted as a marker of coronary microvascular dysfunction when epicardial coronary stenosis is absent. There are no data regarding the relationship between serum Klotho levels and disorders in coronary microcirculation in healthy adults. We aimed to investigate the association between serum Klotho levels and alterations in coronary microcirculation in healthy adults using echocardiographic measurements of CFR. METHODS: Thirty-four healthy volunteers (median age: 34 [27-39], 14 males) were enrolled in this study. The study population was divided into two subgroups according to the median value of serum Klotho levels: a high Klotho (HK) group (n = 17, median age: 34 [30-38]; 6 males) and a low Klotho (LK) group (n = 17, median age: 32 [26-39]; 8 males). The analysis of coronary flow velocities was performed by transthoracic Doppler echocardiography. RESULTS: Hyperemic diastolic peak flow velocities and CFR were significantly higher in the HK group than in the LK group (70 [66-92] versus 61 [47-66], P = 0.003 and 3.0 [2.6-3.8] versus 2.2 [1.7-2.8], respectively, P = 0.001). Serum Klotho levels were positively correlated with CFR (P < 0.001). CONCLUSION: Serum Klotho levels correlate with CFR in a healthy population. Low serum Klotho levels may potentially identify patients with impaired CFR.

Low Serum Level of Klotho Is an Early Predictor of Atherosclerosis.

The Klotho gene, identified as an 'aging suppressor' gene, encodes a single-pass transmembrane protein. The extracellular domain of Klotho is cleaved and released in the blood stream, where it may function as a vasculoprotective hormone. Carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD) of the brachial artery and epicardial fat thickness (EFT) have been reported as early predictors of atherosclerosis. We aimed to investigate the relationship between serum Klotho levels and early atherosclerotic predictors, including EFT, FMD and CIMT in healthy adults. Fifty healthy volunteers were enrolled in this study, consisting of 21 males and 29 females with median age of 32 years. They were free of known risk factors for cardiovascular diseases. Serum Klotho levels were determined by the ELISA method. The study population was divided into two groups (n = 25 for each) according to the median serum Klotho level (459.4 pg/mL): higher Klotho (HK) group (613.6 pg/mL; ranges of 501.2-772.6 pg/mL) and lower Klotho (LK) group (338.7 pg/mL; ranges of 278.8-430.3 pg/mL). EFT was measured by transthoracic echocardiography, and CIMT and FMD were measured with standard procedures. The LK group showed lower values of FMD (p = 0.012) and larger values of EFT (p = 0.01) and CIMT (p < 0.001), compared to the HK group. Thus, the low serum Klotho levels were associated with increased EFT and CIMT and with the decreased FMD in the study population. We propose that the lower serum Klotho level is a newly identified predictor of atherosclerosis.

Retrobulbar blood flow and carotid intima-media thickness alteration may relate to subclinic atherosclerosis in patients with chronic inflammatory diseases.

OBJECTIVE: AA amyloidosis occurs in the setting of longstanding inflammation. An increased incidence of coronary artery disease (CAD) was noted in patients with chronic inflammatory disease (CID). Retrobulbar blood flow predicts future macrovascular events including CAD. Increase in carotid artery intima-media thickness is regarded as a marker for early atherosclerosis. The relationship between chronic inflammation and atherosclerosis is well known; however, the connection between amyloidosis-advanced CIDs and retrobulbar microvascular function and carotid intima-media thickness (CIMT) is unidentified. We aimed to investigate whether retrobulbar microcirculation and CIMT were impaired or not in amyloidosis-advanced CID patients compared to normal subjects. METHODS: Fourteen patients with renal AA amyloidosis and a group of healthy volunteers were included in the study. Measurement of CIMT and retrobulbar blood flow velocities was performed with ultrasound scanner and color Doppler ultrasonography. RESULTS: The CIMT of patients with renal amyloidosis was significantly thicker than that of the normal population (p < 0.001). The resistivity index of the ophthalmic artery (OA) of patients with renal amyloidosis was significantly higher than the study group (p < 0.001). CONCLUSION: This study demonstrates that accelerated atherosclerosis which can be shown by increased OA resistivity index and CIMT are found in amyloidal-related CID patients.

Is serum Klotho protective against atherosclerosis in patients with type 1 diabetes mellitus?

OBJECTIVE: Klotho deficiency is associated with several metabolic disorders. Two dimensional (2D) longitudinal strain (LS) of left ventricle (LV), carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD) of brachial artery and epicardial fat thickness (EFT) have been reported to be early predictors of atherosclerosis. We aimed to investigate the relationship between serum Klotho levels and these early predictors of atherosclerosis in patients with type 1 diabetes mellitus (DM). METHODS: The study included 45 type 1 diabetic patients and 35 controls. Serum Klotho levels were determined by ELISA method. The patient group was also divided into two subgroups according to serum Klotho levels: high (HK) and low Klotho (LK) groups. EFT, CIMT and FMD were measured according to appropriate recommendations. Speckle tracking analysis was performed using the Echopac software. RESULTS: The patient group had significantly lower serum Klotho (p=0.001), FMD (p<0.001) and LS of LV (p<0.001) values, but larger EFT (p<0.001) and CIMT (p<0.001) values than controls. LK subgroup had also significantly lower FMD (p<0.001) and LS of LV (p<0.001) but larger EFT (p=0.002) and CIMT (p<0.001) values than HK subgroup. CONCLUSION: Serum Klotho may have a protective effect against atherosclerosis and endothelial dysfunction in type 1 DM.