Association of the Serum Endostatin Level, Renal Function, and Carotid Atherosclerosis of Healthy Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS).

AIM: To analyze associations among the serum endostatin level, renal function, and carotid atherosclerosis of healthy residents of Japan. METHODS: Among 1,057 Japanese residents who attended free public physical examinations between 2010 and 2011, we evaluated the data of 648 healthy residents (200 men and 448 women, age 24 to 84 years) for whom the serum endostatin level and common carotid intima-media thickness (IMT) were measured. Renal function was assessed by estimated glomerular filtration rate (eGFR). Multiple linear regression analysis was done to determine the association of eGFR and serum endostatin level after adjustment for known covariates. Mediation analysis was done using Baron and Kenny's regression approach. RESULTS: The median endostatin level was 63.7 ng/mL (interquartile range: 49.7-93.2). The mean eGFR was 78.4±14.8 mL/min/1.73m2. Univariate analysis showed that age (r=－0.37, P＜0.01), non current smoking (85.8±13.0 vs. 77.5±14.8 mL/min/1.73 m2, P＜0.01), hemoglobin A1c (r=－0.08, P=0.05), low-density lipoprotein-cholesterol (r=－0.13, P＜0.01), uric acid (r=－0.15, P＜0.01), carotid IMT (r=－0.11, P＜0.01), and log-transformed endostatin (r=－0.36, P＜0.01) were significantly associated with eGFR. In multiple linear regression analysis, log-transformed endostatin was significantly associated with eGFR (beta=－0.24, P＜0.01). While, carotid IMT was no longer significant. Mediation analysis showed serum endostatin level to be a mediator in the association between carotid IMT and eGFR. CONCLUSIONS: The association between carotid IMT and eGFR is mediated by the serum endostatin level of healthy individuals.

Correlation between Thyroid Stimulating Hormone and Renal Function in Euthyroid Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS).

AIM: The present large-scale Japanese population study was performed to evaluate the relation between the serum thyroid stimulating hormone (TSH) level and renal function. METHODS: Out of 1,374 residents who participated in a free public physical examination between 2010 and 2011, we evaluated the data of 888 participants for whom the serum TSH level and estimated glomerular filtration rate (eGFR) were successfully measured. The participants were categorized into three groups based on TSH levels (normal TSH, ≤2.4; high-normal TSH, 2.5-4.4; and subclinical hypothyroid, ≥4.5 µIU/mL). Multiple linear regression analysis adjusted for cardiovascular risk factors was performed to determine the relationship between serum TSH level and renal function. RESULTS: The mean±SD TSH level was 2.0±1.4 µIU/mL, and 75.9% (n=674) of the participants had normal, 17.9% (n=159) had high-normal, and 6.2% (n=55) had subclinical hypothyroid TSH levels. The mean eGFR significantly decreased with increased TSH levels (normal TSH, 79.3±14.1; high-normal TSH, 77.4±13.0; and subclinical hypothyroid, 72.3±12.2 mL/min/1.73 m2: P for trend ＜0.01). Multiple linear regression analysis extracted log-transformed TSH level as an independent factor correlated with eGFR in the high-normal TSH group (beta=-0.18, P=0.02). CONCLUSIONS: Our findings demonstrated a significant correlation between serum TSH levels and eGFR in high-normal TSH participants. In healthy individuals, high-normal TSH levels indicate increased the risk of chronic kidney disease.

The Relation between Serum Endostatin Level and Carotid Atherosclerosis in Healthy Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS).

AIM: To examine the association between the serum endostatin levels and subclinical atherosclerosis independent of traditional risk factors in a healthy Japanese population. METHODS: Among 1,057 residents who attended free public physical examinations between 2010 and 2011, we evaluated the data of 648 healthy residents for whom the serum endostatin level and common carotid intima-media thickness (IMT) were successfully measured. RESULTS: The median endostatin level was 63.7 ng/mL (interquartile ranges: 49.7-93.2 ng/mL), and the mean carotid IMT was 0.68±0.12 mm. Residents with above median endostatin had significantly higher carotid IMT than did those with below median endostatin (0.71±0.14 vs. 0.65±0.09 mm, P＜0.001). Multiple linear regression analysis demonstrated that increased serum endostatin is significantly associated with carotid IMT (above vs. below median endostatin level; beta=0.11, P=0.03), independent of the known covariates of age, sex, body mass index, drinking and smoking status, systolic blood pressure, diastolic blood pressure, hemoglobin A1c, low density lipoprotein cholesterol, estimated glomerular filtration rate, and log-transformed high sensitive C-reactive protein. CONCLUSIONS: A higher serum endostatin level reflected subclinical atherosclerosis in this Japanese population.