Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study design was approved by the Institutional Review Board of Tri-Service General Hospital, Taipei, Taiwan. All participants signed an informed consent form. The information obtained was used for research purposes only. Data were analyzed anonymously.
Study population
From 2007 to 2015, 44,563 participants, who were healthy according to a survey conducted by the Health Management Center of Tri-Service General Hospital (a medical center in Taipei, Taiwan), were included in our study. To reduce confounding effects, we excluded individuals (n = 32,370) with a history of dyslipidemia, coronary artery disease, hypertension, DM, hepatobiliary disease, pancreatitis, or malignancy (including pancreatic cancer, ovarian cancer, and other malignancies), and those on any medication. Subjects (n = 10,443) lacking data on MetS components, lipid profiles, blood biochemistry tests, tumor marker tests, medical history, and physical examinations were also excluded.
This study involved 1,750 participants with no known medical history or chronic illness (Fig. 1). Participants were divided into three groups based on their CA19-9 levels. The CA19-9 tertiles were as follows: T1 (≤ 6.58 U/mL); T2 (6.59–12.99 U/mL); and T3 (13–143 U/mL).
General characteristics and laboratory measurements
Information regarding the participants’ medical history was obtained by questionnaire. Physical examinations were performed by experienced physicians. BMI was estimated using equation (1):
WC was measured to the nearest centimeter using a constant tension tape at the level of the umbilicus while the participants were in the standing position. Blood pressure was measured using an automatic electronic sphygmomanometer while the participants were in the sitting position, after resting for 5 minutes.
Blood samples were collected after fasting for > 8 hours via vacuum blood collection tubes containing EDTA. Serum biochemical parameters, such as TG, total cholesterol (TC), blood urine nitrogen (BUN), uric acid (UA), creatinine, C-reactive protein (CRP), HDL, low-density lipoprotein (LDL), albumin, and fasting plasma glucose, were measured using an automatic analyzer. The tumor marker, CA19-9, was measured using RIA.
Definition of MetS
According to the revised National Cholesterol Education Program’s Adult Treatment Panel III[33], MetS was defined by the presence of at least three of the following parameters: WC ≥ 90 cm in men or ≥ 80 cm in women; serum TG ≥ 150 mg/dL (1.7 mmol/L); HDL ≤ 40 mg/dL (1.03 mmol/L) in men or ≤ 50 mg/dL (1.29 mmol/L) in women; SBP ≥ 130 mmHg or diastolic blood pressure (DBP) ≥ 85 mmHg; and fasting plasma glucose ≥ 100 mg/dL (5.6 mmol/L).
Statistical analyses
Statistical analyses were performed using SPSS Statistics (released 2009) (PASW Statistics for Windows, version 18.0; SPSS Inc., Chicago, IL, USA). Continuous variables are expressed as mean ± SD, whereas categorical variables are expressed as numbers and percentages. The association between CA19-9 and incident MetS was evaluated using Cox regression models. An extended model approach was used to adjust for covariates. Model 1 was not adjusted for any covariates. Model 2 was adjusted for sex, age, and BMI. Model 3 was adjusted for the covariates in Model 2 and TC, BUN, creatinine, UA, albumin, and CRP.