The methods of Ahn et al. were grossly referenced in this study28. This study was approved by the Institutional Review Board (IRB) of Kim’s Eye Hospital (IRB number KEH 2022-04-008), and was conducted according to the principles of the Declaration of Helsinki. The need for informed consent was waived by the IRB of Kim’s Eye Hospital because the study did not include any identifiable information about the subjects. The Korean National Health Insurance Corporation has allowed authors to use the database based on the approved IRB.
Study Design And Data Sources
The data analyzed in this study were derived from the National Health Information Database (NHID), which includes all data from the NHIS covering the entire population of the Republic of Korea. Briefly, all insured Korean adults, except 3% of the population covered by the Medical Aid program, were recommended to undergo standardized biennial medical examinations consisting of detailed surveys of demographics, medical histories, lifestyle questionnaires, vital signs, anthropometric measurements, and laboratory tests. In addition to the regular health examination records, the Korean NHIS collects sociodemographic data, income-based insurance contributions, prescription records, inpatient and outpatient usage, and the date of death of all insured Koreans in the NHID 29,30.
A total of 1,571,091 adults aged ≥ 20 and < 40 years who underwent four serial health examinations between January 1, 2009, and December 31, 2012, were selected from the NHID. The database was collected over four consecutive years from the first health examination. Individuals with a history of RVO, missing health examination data or covariates, or with a diagnosis of RVO within one year from the last health examination (index date) were excluded (Fig. 2). Ultimately, 1,408,093 adults were included in the analysis.
Evaluation Of Metabolic Syndrome And The Influence Of Cumulative Metabolic Burden
The MetS was defined using the modified waist circumference criteria of the Korean Society for the Study of Obesity and the guidelines of the National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) as the presence of ≥ 3 of the following: increased WC [≥ 90 cm in males or ≥ 85 cm in females], elevated TG [≥ 150 mg/dL (1.7 mmol/L) or drug treatment for elevated TG], low HDL-C [< 40 mg/dL (1 mmol/L) in males and < 50 mg/dL (1.3 mmol/L) in females or drug treatment for low HDL-C], elevated blood pressure [systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg or current use of antihypertensives], and impaired fasting glucose [fasting plasma glucose ≥ 100 mg/dL (5.6 mmol/L) or current use of anti-diabetes] 31–33.
At each health examination, the presence of MetS and the number of fulfilled MetS components were calculated. “Metabolic burden” was defined in the following ways during four health examinations: (1) cumulative number of MetS diagnosed at each health examination (0–4 times); and (2) cumulative number of each MetS component diagnosed at each health examination (0–4 times per MetS component).
Covariates, Follow-up, And Clinical Outcomes
The baseline characteristics of the individuals were designated as the data of the last health examination (index date), which comprised sociodemographic data, income-based insurance contributions, laboratory results, anthropometric measurements, comorbidities (diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease), and answers to lifestyle questionnaires. We investigated the risk of new-onset RVO using the International Classification of Diseases, Tenth Revision (ICD-10) codes and inpatient and outpatient records. The follow-up period was the time from the index date to the occurrence of RVO or December 31, 2018, whichever occurred first.
Statistical analysis
Data are summarized as mean ± standard deviation for continuous variables and number (%) for categorical variables. One-way analysis of variance and the chi-square test were used to evaluate significant differences in baseline characteristics among groups categorized by the number of MetS components. The incidence rate of RVO was computed by dividing new-onset RVO cases by the total follow-up duration and was presented as per 1000 person-years (PY). The association between MetS status frequency and RVO incidence was estimated using Cox proportional hazards regression models. The risk of RVO according to the number of patients with MetS compared with the non-MetS group was expressed as HRs with 95% CIs. Model 1 represented an unadjusted risk, and Model 2 was adjusted for age and sex. Model 3 was adjusted for age; sex; smoking status (never smoker, ex-smoker, or current smoker); alcohol intake (non-, mild, or heavy drinker, g/day); regular exercise (performing > 30 min of moderate physical activity ≥ 5 times a week or > 20 min of vigorous physical activity ≥ 3 times a week); and low-income level (income in the lower 20% of the entire Korean population of subjects supported by the medical aid program)34. Model 4 was additionally adjusted for systolic blood pressure, fasting glucose, the logarithm of TG, and HDL-C levels. A P value of less than 0.05 was considered statistically significant. Data collection and statistical analysis was performed using SAS version 9.4 (SAS Institute, Cary, NC).