Study population
Our study population (n = 44,066) consisted of individuals involved in a comprehensive health screening program that included NT-proBNP level measurement and abdominal US at Kangbuk Samsung Hospital, Seoul, Korea, from 2016 to 2018. The screening program aimed to promote health through early detection of chronic diseases and their risk factors. Additionally, the Korean Industrial Safety and Health Law requires employees to participate in an annual or biennial health examination. To minimize the effect of disease or medication on NT-proBNP levels, we excluded 4,143 subjects due to: hypertension (n = 2,180), coronary disease (n = 140), diabetes (n = 821), history of cancer (n = 1,285), NT-proBNP > 18,000 (n = 3) and missing information (n = 193). Some participants met multiple conditions of exclusion, and 39,923 participants were included in the final study.
Measurements
Data on demographic variables, health behaviors, educational background, past medical history and family history of CVD were collected using standardized, self-administered questionnaires (9). Anthropometric measurements and vital statistics were obtained by professional staff. The questionnaire asked about the frequency of alcohol consumption and the amount of alcohol consumed per consumption day recorded in standard units (10).
Following a minimum of 10 h of fasting, blood samples were obtained and analyzed in a single clinical core laboratory. The core clinical laboratory is certified by the Korean Association of Quality Assurance for Clinical Laboratories. Serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured using Bayer Reagent Packs (Bayer Diagnostics, Leverkusen, Germany) on an automated chemistry analyzer (Advia 1650 Autoanalyzer; Bayer Diagnostics). Serum NT-proBNP levels were determined using an automated immunoassay analyzer (cobas e411; Roche Diagnostics, Tokyo, Japan). The inter-assay coefficients of variation for quality control specimens of lower levels and higher levels were 1.20–5.37% and 2.28–4.33%, respectively, during the study period.
The diagnosis of FL was based on abdominal US operated by experienced radiologists who were blinded to the aim of the present study. Ultrasonographic diagnosis of FL was determined based on standard criteria, including a diffuse increase of fine echoes in the liver parenchyma compared with kidney or spleen parenchyma, deep beam attenuation and bright vessel walls (11). The HOMA-IR was calculated as fasting insulin (mg/dL) x fasting glucose (mg/dL)/405. Individuals with HOMA-IR in the top quartile were considered to have IR (12). Obesity was defined as BMI ≥25 kg/m2 in this Asian population.
Statistical analysis
Data are expressed as means [standard deviation (SD)] or as median (interquartile ranges) for continuous variables. Categorical data are expressed as numbers and percentages. Baseline variables were compared using Student’s t-test, Wilcoxon rank-sum test or chi-square test as appropriate. Skewed variables were transformed into log2 to facilitate interpretation. Regression analyses were repeated using generalized linear models to accommodate variables (FL, HOMA-IR index and BMI) with log2-transformed NT-proBNP, using non-FL and low HOMA-IR index as the reference. Multivariate model 1 was adjusted for age, sex, waist circumference, systolic blood pressure, smoking status, physical activity, alcohol consumption, educational level and estimated glomerular filtration rate. To assess whether the association between FL and NT-proBNP level is mediated by IR, model 2 was adjusted for the variables in model 1 and BMI and HOMA-IR index. Reported p values were two-tailed, and < 0.05 was considered statistically significant. All statistical analyses were conducted using STATA version 16.1 (StataCorp LP, College Station, TX, USA).
Ethical considerations
This study was approved by the Institutional Review Board of Kangbuk Samsung Hospital, which exempted the requirement for informed consent because only retrospectively accessed de-identified data were utilized.