Materials and Methods
From 2005 to 2009, a total of 2904 individuals participated in a CV health survey program at a tertiary medical center in Taipei, Taiwan. Patients provided serum used to measure thyroid hormones and other clinical data, such as the results of MDCT imaging. To avoid prospective confounding effects on thyroid functions, we excluded individuals who had 1) malignant disease, 2) an abnormal liver function test (glutamic oxaloacetic transaminase/glutamic pyruvic transaminase levels that were 2-fold more than the upper normal limits, 3) an abnormal renal function test (serum creatinine > 1.5 mg/dL), 4) a history of thyroid disease, or 5) were taking thyroxine or an antithyroid drug (Figure 1).
After exclusion, a total of 1519 EU and 125 SCH participants (age: 49.5 ± 9.8 years; 29.0% females; age: 52.9 ± 10.2 years; 41.6% females) remained for analysis. The study protocol was granted MacKay Memorial Hospital Institutional Review Board Approval of Clinical Trial (No. 18MMHIS137), and all participants gave written informed consent.
A detailed physical examination and a thorough review of the baseline characteristics and medical history were performed using structured questionnaires. A history of hypertension (HTN) was defined as systolic blood pressure (SBP) higher than 140 mm Hg, diastolic blood pressure higher than 90 mm Hg, or a previous diagnosis of HTN with current medications. A history of DM was defined as a fasting glucose level greater than 126 mg/dL, or glycated hemoglobin A1c more than 6.5%, or the current use of any diabetic medication for treating previously diagnosed DM.
Baseline Anthropometric Measurements
All baseline characteristics and anthropometric measurements, including age, body height, body weight (BW), BMI, and WC, were collected. Height was measured by using a standard stadiometer. Weight was measured in light clothes by using a set of standard calibrated electronic scales. The WC and hip circumference were measured using a constant-tension tape. WC was measured at the midpoint between the lowest rib and the upper point of the iliac crest and at the end of normal expiration. Standardized sphygmomanometer cuff-defined resting blood pressure values were measured while resting. Anthropometric measurements such as height, weight, WC, hip circumference, and blood pressure were examined and recorded by trained nurses who were blinded to the patient's information in a laboratory center.
Laboratory Data Acquisition and Analysis
To measure TSH and free thyroxine (FT4), serum was collected after 12 hours of fasting and prior to MDCT. FT4 and TSH (DiaSorin) were quantified by immunoradiometric assay using a commercially available kit. Because all participants had been ruled out for acute or severe health problems, the potential confusion of nonthyroidal diseases would be ignored. Participants were asked to discontinue medications and stop consuming food approximately 24 hours prior to blood collection to greatly reduce thyroid function interference.
A Hitachi 7170 Automatic Analyzer (Hitachi Corp) was used to measure the levels of fasting glucose, glycated hemoglobin A1c (hexokinase method), total cholesterol, LDL-C and HDL-C (homogenous enzymatic colorimetric assay), and TGs.
Classification Based on Thyroid Function and Framingham Risk Score
The reference ranges for FT4 and TSH were 1.0 to 1.71 ng/dL, and 0.4 to 4.0 mIU/mL, respectively. In the SCH group, serum levels ranged from 4.1 to 10.0 mU/L, and those in the EU group were between 0.5 and 3.9 mU/L. The serum FT4 level in the SCH and EU group was in normal range.[4,5]
The 10-year Framingham risk score (FRS), a point system based on age, sex, SBP, TC, HDL-C, and smoking, was calculated according to the National Cholesterol Education Program guidelines. The absolute risk of a CV event in 10 years (AR10y) was divided into 3 FRS categories: low risk (< 10%), intermediate risk (10%-20%), and high risk (> 20%).[10,27]
The CVAI score was calculated using the specific formula for the Chinese population:
Men: CVAI = −267.93 + 0.68 × age + 0.03 × BMI + 4.00 × WC + 22.00 × log10 (TG) − 16.32 × HDL
Women: CVAI = −187.32 + 1.71 × age + 4.23 × BMI + 1.12 × WC + 39.76 × log10 (TG) − 11.66 × HDL
ABSI was calculated as WC/(BMI2/3 × height1/2) and expressed in m11/6kg−2/3.
BRI = 364.2 – 365.5 × (1 – [WC/2π]2/[0.5 × height2)½
BMI was calculated as weight/height squared (kg/m2).
Multidetector Computed Tomography Scanning Protocol
Scanning was performed using a 16-slice MDCT scanner (Sensation 16; Siemens Medical Solutions) with 16- × 0.75-mm collimation, rotation time of 420 ms, and tube voltage of 120 kV. During one breath-hold, images were acquired from above the level of tracheal bifurcation to that below the base of the heart by using prospective electrocardiogram-triggering with the center of the acquisition at 70% of the R-R interval. Using the raw data, the images were reconstructed with standard kernel in 3-mm thick axial nonoverlapping slices and a 25-cm field of view.
Measurements of Pericardial Fat and Thoracic Periaortic Fat
The VATs of PCF and TAT were quantized at a dedicated workstation using an MDCT (Aquarius 3D Workstation). The semiautomatic segmentation technique was implemented for quantification of fat volumes. We traced the region of interest manually and defined the fat tissue as pixels within a window of −195 to −45 HU and a window center of −120 HU. PCF was defined as the volume-based burden of total adipose tissue located within the pericardial sac (Figure 2A). The TAT tissue was defined as the total adipose tissue volume surrounding the thoracic aorta (as periaortic fat), which extends 67.5 mm from the level of bifurcation of the pulmonary arteries (Figure 2B) with cranial-caudal coverage of the thoracic aorta.
Multidetector computed tomography demonstrated pericardial and thoracic periaortic fat tissue measures. A, Pericardial adipose tissue: the fat between the heart and the pericardium. B, Thoracic periaortic adipose tissue: the fat surrounding the thoracic aorta (shown in axial view) . Orange regions indicate visceral fat tissue.
Reproducibility for Multidetector Computed Tomography-derived Visceral Adiposity
The reproducibility of PCF and TAT was evaluated by performing repeated measurements of 40 randomized cases with the initial results and clinical data blinded between readers and has been published before. The intraobserver and interobserver coefficients of variation for PCF were 4.27%, 4.87% and 6.58%, 6.81% for TAT, respectively.
Continuous variables are expressed as the mean ± SD or median values (interquartile range), whereas categorical variables are presented as absolute values and percentages. The independent t test was used to test for differences in normally distributed continuous variables and the Mann-Whitney U test was used for comparisons involving abnormally distributed variables. Categorical variables were compared with the chi-square test or Fisher exact test as appropriate. Pearson correlation analysis was used to evaluate the correlations between 5 anthropometric indices and metabolic parameters, age, and thyroid function. Multivariable logistic regression models were performed to estimate the odds ratios (ORs) and 95% CI of SCH associated with these 5 indices in 4 models for men and women (model 1: unadjusted; model 2: adjusted for age; model 3: adjusted for factors in model 2 plus smoking; amodel 3 means: adjusted for factors in model 2 plus smoking and BMI; model 4: adjusted for factors in model 3 plus SBP, FPG, HDL-C, LDL-C, and FRS); and 3 models in different CV risks groups (model 1: unadjusted; model 2: adjusted for age and smoking; * means model 2: adjusted for age, smoking, and BMI; model 3: adjusted for factors in model 2 plus SBP, FBG, LDL-C, and HDL-C), respectively. A P value less than .05 was considered statistically significant, and all analyses were performed using the SPSS 15.0 statistical package (SPSS Inc).
J Endo Soc. 2021;5(6) © 2021 Endocrine Society