Study design and population study
The current study was performed within the framework of the TLGS, which is an ongoing cohort study being conducted on a representative sample of Tehranian citizens. The TLGS have the aim of determining the epidemiological aspects of non-communicable diseases (NCDs) and their risk factors. The TLGS also intended to prevent NCDs by developing healthier lifestyles. Further details for the TLGS have been described before [10]. Briefly, after the first baseline examination (1999-2001), participants were followed-up until 2011. For this study, 8,400 individuals aged ≥30 years were enrolled from phase IV of TLGS (2008-2011). Firstly, we excluded 497 individuals whose glycemic status was not differentiable for us. Secondly, we excluded 177 subjects with missing data on covariates, including body mass index (BMI), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), family history of CVD, and smoking status (overlap features between numbers considered). Finally, due to the lack of information on the outcome (CHD) assessment, eight individuals were excluded, and 7,718 participants remained eligible for analysis of the current study.
Clinical and laboratory measurements
Using pretested questionnaires, an interviewer gathered data that included demographic data, smoking status, education level, drug history, past medical history, and family history. Details of blood pressure (BP) and anthropometric parameters measurements in the TLGS setting have been published previously [11]. After over 12 hours of fasting, blood samples were drawn between 07:00 AM and 09:00 AM and then analyzed on the same day. Apart from those who had on glucose-lowering medications, a standard oral glucose tolerance test with 75 gr glucose was done for all participants. Fasting plasma glucose (FPG) and 2-hour post-challenge plasma glucose (2h-PCPG) were measured by enzymatic colorimetric glucose oxidase method, both inter-and intra-assay coefficient of variations were < 2.2%. More details of laboratory measurements have been published elsewhere [11].
Definition of terms
Participants were categorized into different groups as follows: Normal fasting glucose (NFG)/normal glucose tolerance (NGT), FPG < 5.6 and 2h-PCPG <7.7 mmol/L; isolated impaired fasting glucose (iIFG), 5.6 ≤ FPG ˂ 7 and 2h-PCPG <7.7 mmol/L; isolated impaired glucose tolerance (iIGT), 7.7 ≤ 2h-PG ˂ 11.1 and FPG <5.6 mmol/L; combined IFG and IGT (IFG/IGT), 5.6 ≤ FPG ˂ 7 and 7.7 ≤ 2h-PCPG ˂ 11.1 mmol/L [12]. Moreover, in the present study, prediabetes status was defined as the presence of IFG or IGT. Finally, newly diagnosed diabetes mellitus (NDM) was defined as FPG ≥ 7.0 or 2h-PCPG ≥ 11.1 mmol/L among those participants were not on glucose-lowering medications and known diabetes mellitus (KDM) as subjects with positive history of taking any glucose lowering medications. Having TC≥ 5.2 mmol/L or using lipid-lowering medications defined as hypercholesterolemia. Low HDL-C was defined as HDL-C< 1.036 mmol/L for men and <1.295 mmol/L for women, or taking lipid-lowering medications. Based on the seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (the JNC 7 report) [13], hypertension was considered as either of having SBP ≥140 mmHg or DBP ≥90 mmHg or the usage of any anti-hypertensive medications. Smoking status was categorized into three levels, including current, past, and never smoker. Education levels were classified as <6 years (reference group), 6–12 years, and >12 years. By the Modifiable Activity Questionnaire (MAQ), which judged all types of activities [11], physical activity was evaluated. Low physical activity (inactive person) was defined as not achieving a minimum score of 600 MET (metabolic equivalent task)-minutes per week [14]. If there was at least one history of CHD/stroke in a male first-degree relative aged <55 years or in a female first-degree relative aged <65 years, the family history of premature CVD is considered positive.
Definition of CHD
Details of the collection of outcome data have been reported elsewhere [11]. To summarize, each individual was under continuous surveillance for any medical outcome leading to hospitalization. As a part of the cohort data collection, a trained nurse called all participants annually and recorded any medical events experienced during the last year. A trained physician followed-up any reported event by a home visit for medical data gathering. Collected data were then evaluated by a consulting committee, the outcome committee, included a principal investigator, an internist, an endocrinologist, a cardiologist, an epidemiologist, and the physician that collected the outcome data. Every confirmed event was considered as a NCD outcome based on ICD-10 criteria [11, 15]. In this study, CHD was selected from ICD-10 rubric I20-I25. CHD cases included [15-18]:
(1) Myocardial infarction (MI), included a) definite MI diagnosed by diagnostic electrocardiogram (ECG) and biomarkers (including CK, CK-MB, CK-MBm, troponin (cTn), and myoglobin), b) probable MI distinguished by positive ECG findings plus cardiac symptoms or signs and biomarkers showing negative or equivocal results.
(2) Cardiac procedure, defined as a) angiography proven CHD with a result of ≥ 50% stenosis in at least one major coronary vessel, b) history of angioplasty or bypass surgery.
(3) Unstable angina pectoris, who developed new cardiac symptoms or showed changing symptom patterns and positive ECG findings with normal biomarkers and admitted to coronary care unit (CCU).
Statistics
Baseline characteristics are presented as means ± standard deviations (SD), median (interquartile range), and number (frequency) as appropriate. ANOVA and Kruskal-Wallis tests were used for comparison of means and medians, respectively. Chi-squared test was applied for comparison of frequencies.
The crude and age-standardized prevalence (95% confidence interval: CI) were calculated for all glycemic status, including NFG/NGT, iIFG, iIGT, IFG/IGT, NDM, and KDM. Regarding differences in the age distributions between the TLGS population from 2008 to 2011 and the Iranian census 2010 (supplementary Table 1), especially in the 30-39-year age-group and those aged ≥70 years, the age-standardized prevalence was reported, using the Iranian (Tehran province) census 2010.
We also examined the association of different glycemic status with the prevalence of CHD. Using logistic regression analyses, odds ratios (ORs) for this association were calculated in 3 levels of adjustment: 1) without adjustment (crude OR); 2) age and sex adjustment; 3) full adjustment (adjusted for age, sex, BMI, hypercholesterolemia, low HDL-C, hypertension, family history of premature CVD, and smoking status).
Statistical analyses were done using STATA version 14. P-values < 0.05 were considered to be statistically significant.