BMI category-specific waist circumference thresholds based on cardiovascular disease outcomes and all-cause mortality: Tehran Lipid and Glucose Study (TLGS)

doi:10.21203/rs.3.rs-2124957/v1

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BMI category-specific waist circumference thresholds based on cardiovascular disease outcomes and all-cause mortality: Tehran Lipid and Glucose Study (TLGS)

https://doi.org/10.21203/rs.3.rs-2124957/v1

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published 05 Jul, 2023

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Background

Waist circumference (WC) is representative of abdominal visceral fat, which is strongly associated with cardiovascular disease (CVD) and its’ outcomes. We aimed to define WC thresholds predicting incident CVD and all-cause mortality within each body mass index (BMI) categories in Tehran Lipid and Glucose Study.

Methods

In this prospective cohort study, a total of 3344 men and 4068 women were followed up for 18 years. Participants were categorized based on BMI into BMI < 25, 25 < BMI < 30, and BMI > 30. The sex-specific WC cut-points within each group were estimated by the maximum value of Youden’s index based on incident CVD and all-cause mortality prediction.

Results

667 and 463 CVD incidents (incident rate 3.1 to 4.5 in men and 1.1 to 2.6 in women per 1,000 person-years within BMI categories) and 438 and 302 mortalities (incident rate 2.1 to 2.7 in men and 1.2 to 1.4 in women per 1,000 person-years within BMI categories) were happened in men and women, respectively. WC thresholds were 82, 95, and 103cm based on incident CVD and 88, 95, and 103cm based on all-cause mortality among men in BMI < 25, 25 < BMI < 30, and BMI > 30, respectively. The respective values for women were 82, 89, and 100cm based on incident CVD and 83, 90, and 99cm based on all-cause mortality in BMI < 25, 25 < BMI < 30.

Conclusion

The BMI-specific WC thresholds given here can give clues to future studies to define more accurate incidence-based WC cut-offs as screening tools to better identify individuals at high risk of developing CVD.

Obesity is known as a public health issue worldwide (1). It is also known as a modifiable major cardiovascular (CVD) risk factor (2). The prevalence of obesity increased remarkably in recent years in developing and developed countries (3). A 33-years long evaluation until 2013 demonstrated that national measurements against obesity in no country were successful (4). The national obesity trend in Iran revealed thatoverall obesity prevalence increased from 13.6–22.3% from 1999 to 2007 (5). Also, based on the results of the Tehran Lipid and Glucose Study (TLGS), the prevalence of obesity and abdominal obesity in Tehran, capital of Iran, in a 12 years follow-up from 1999 to 2011, increased from 23.1% and 47.9% at baseline to 34.1% and 71.1% at the end of follow-up, respectively (6).

Waist circumference (WC) is an anthropometric variable that can easily be measured using simple equipment. Despite body mass index (BMI) that only represents total body fat amount, WC is a significant predictor of abdominal visceral fat and total body fat (7). The association of abdominal visceral fat with CVD incidence was stronger than the total body fat, evaluated by BMI measurement (8). WC was strongly associated with the incident of metabolic syndrome (9), all-cause mortality, and CVD (10–12) Although WC is considered as an independent risk factor for CVD and its’ mortality(13), the predictive value of WC after adjustment for BMI gets stronger (12–14).

In different BMI categories, health problems increase from the normal weight group to the obesity group. Also, in each BMI category, the risk of CVD and mortality was higher among the ones with higher WC.(15, 16) A wide range of WC cut-points utilizing different methodologies has been suggested. WC thresholds should be specific to different populations and ethnic groups, and a single threshold cannot apply to all populations (17). The most commonly used WC cut-point of white Caucasians in current guidelines is ≥102cm for men and ≥88cm for women, which is a sex-specific equivalent to BMI = 30 (18). Several studies suggested different sex-specific cut-off values of WC based on cardiometabolic risk factor prediction (19–21), and a few were based on CVD outcomes (22, 23), while many of them were cross-sectional studies. Defining WC cut-offs in each BMI category was associated with increased sensitivity and specificity in predicting cardiometabolic risks (24). Also, predicting mortality based on WC cut-offs in BMI categories was enhanced compared to single-sex specified cut-off (25).

In this prospective cohort study in the framework of TLGS, we evaluated the association between WC and CVD incidence. We attended to determine BMI category-specific WC thresholds based on CVD outcomes and all-cause mortality. The results of this study will help us better identify the patients with higher risks in the clinic to plan an effective intervention in individual and community scales.

Study population:

In this prospective cohort study, the subjects were driven from TLGS, an ongoing community-based prospective study to determine risk factors and outcomes of non-communicable diseases (26). In the TLGS, 15,005 participants were recruited in Phases I and II of the study that were selected through the multistage random sampling method from district 13 of Tehran. All participants were aged≥3 years. The demographic characteristics, clinical properties, biochemical status, anthropometric examinations, and lifestyle data of the participants were updated every three years after the baseline survey that was performed from 1999 to 2001. Further prospective follow-up surveys were held from 2002 to 2005 (Phase II), 2006 to 2008 (Phase III), 2009 to 2011 (phase IV), 2012 to 2015 (Phase V), and 2016 to 2019 (Phase VI).

From the TLGS overall group, 9559 participants, aged ³ 30 years, were enrolled in Phases I and II of the study. After excluding participants with a history of CVD at the baseline (n=785), history of cancer (n=43), those taking corticosteroid medication at baseline (n=180), underweight (n=112), and those who had missing data or lost to follow-up (n=1027); we recruited 7412 participants, of which 3344 were men, and 4068 were women. All participants were followed up until 20 March 2018. The median follow-up time was 17.7 years.

Ethical approval:

This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects were approved by the research committee of Shahid

Beheshti University of Medical Sciences. Written informed consent was obtained from all subjects.

Anthropometric and laboratory assessment:

Detailed information protocol and laboratory procedures of the TLGS were published in a previous stud (26). Briefly, all demographic and anthropometric data were collected by trained health care professionals, using established protocols. To measure height, subjects were barefoot in standing position against wall with shoulders in normal alignment, and the tape stadiometer was used. Weight was measured using a digital electronic scale (Seca 707; range 0.1-150 kg, Hanover, MD, USA) while subjects were minimally clothed and barefoot, and the obtained weight was rounded to the nearest 100 g. BMI measured as . WC was measured non-flexible tape meter at umbilical level and without pressure to the body surface while subjects were standing.. Measurements were rounded to the nearest 0.1cm. Systolic and diastolic blood pressures were obtained utilizing a standard mercury sphygmomanometer (calibrated by the Iranian Institute of Standards and Industrial Researches) by a physician at least two times from the right brachial artery at the heart level after subjects rested for 15 minutes.

The blood sample was collected after 12 to 14 hours of fasting, from 7 to 9 am at the TLGS Research Laboratory to measure fasting plasma glucose (FPG) and lipid concentrations. The commercially available laboratory kits (Pars Azmoon Inc, Tehran, Iran) adapted to a Selectra 2 auto-analyzer were utilized. The samples were centrifuged for 30–45 minutes after collection.

We utilized the enzymatic calorimetric method with glucose oxidase for FPG; glycerol phosphate oxidase for triglyceride; and cholesterol esterase and cholesterol oxidase for total cholesterol in the assessment. High-density lipoprotein cholesterol (HDL-C) was measured after precipitation of apolipoprotein B containing lipoproteins with phosphotungstic acid. If TG <400 mg/dl, the low-density lipoprotein cholesterol (LDL-C) was calculated using the Friedwald formula(27). The inter-and intra-assay coefficients of variation (CV) were 0.6 and 1.6%; 0.5 and 2%; 2.2 and 2.2%; 0.5 and 2%; triglyceride, HDL-C, FPG and TC respectively.(26)

Variables Definition:

A family history of CVD was defined as a prior diagnosis of CVD in any first-degree female relative aged <65 or male relative aged <55 years old. Hypertension is diagnosed as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or the current use of antihypertensive medication is present (28). Diabetes mellitus is defined as each of the criteria is present; 1- Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL), 2- Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75-gram oral glucose load, 3- Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) plus symptoms of high blood sugar, 4- the current use of medication is present (29).

Coronary heart disease (CHD) is defined as the presence of 1- definite myocardial infarction (MI); diagnosed by evolving diagnostic electrocardiography (ECG) and positive biomarkers; or, 2- probable myocardial infarction; diagnosed by positive ECG findings plus cardiac symptoms and signs plus missing biomarkers, or Positive ECG findings plus equivocal biomarkers; or, 3- unstable angina pectoris; defined as new cardiac symptoms or changing symptom patterns and positive ECG findings and normal biomarkers; or 4- angiographic proven CHD; or 5- CHD death; including definite and possible fatal MI. CVD is defined as the presence of CHD as defined priorly, or stroke; or cerebrovascular death (30). Cardiovascular mortality is defined as death attributed to MI, heart failure, cardiac arrest due to other or unknown causes, or cerebrovascular accidents (31).

Statistical analysis:

All statistical analyses were stratified by sex. All normally-distributed continuous variables were expressed as mean ± standard deviation (SD). Otherwise, skewed-distributed continuous variables were shown as median and inter-quartile range (IQR) 25-75. Categorical variables of baseline characteristics were shown as frequency (percentages). Differences in characteristics of men and women between BMI categories were tested using analysis of variance (ANOVA), Kruskal-Wallis H, and chi-square test for normal, skewed, and categorical variables, respectively. Cox proportional hazard models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) for incident CVD and all-cause mortality in BMI categories. Cut-points for waist circumference in BMI categories were estimated by the maximum value of Youden’s index. All statistical analyses were performed using STATA version 14 (STATA, College Station, TX); the significance level was set at P<0.05 (two-tailed).

Among all subjects recruited in 1^st and 2^nd phase of TLGS, after excluding subjects with specific criteria, 7412 subjects aged above 30 years old were enrolled, of which 3344 were men (45.1%) and 4068 were women (54.9%). Baseline characteristics and cardiometabolic profiles of men and women participants are presented in Tables 1 and 2, respectively. Of all men, 1264 (37.8%) were normal weight, 1541 (46.1%) were overweight, and 539 (16.1%) were categorized as obese. In contrast, among women, 919 (22.6%), 1708 (42.0%), and 1441 (35.4%) were in the normal weight, overweight, and obesity group, respectively, with a lower rate of normal weight and a higher rate of obese participants among women. The mean WC values were 91.1±10.5 cm in men and 90.7±11.9 cm in women. The participants’ characteristics are compared in different BMI categories. The difference between all variables were significant in both men and women, except for family history of CVD and smoking in women, which the differences were not statistically significant between different BMI categories.

The incidence rate and hazard ratios (per 1cm increase in WC within each BMI category) of incident CVD and all-cause mortality were depicted in Table 3. Of all men, 667 (19.9%) were diagnosed with CVD during the follow-up time, and among women, 463 (11.4%). There were 740 deaths, of which 438 were among men, and 302 happened among women. In men and women, 32% (140 out of 438) and 24.2% (73 out of 302) of all deaths were due to CVD, respectively. The CVD incident rate was increased from normal weight to obesity group in both men (3.1, 4.1, and 4.5 per 1000 person-years in normal weight, overweight and obese men, respectively) and women (1.1, 2.1, and 2.6 per 1000 person-years in normal weight, overweight and obese women, respectively). Also, a higher CVD incident rate was observed among men than women in all BMI categories. The incident rates per 1000 person-years for all-cause mortality were 2.71, 2.07, and 2.16 in men with normal weight, overweight, and obesity, respectively. In contrast, the respective values in women were 1.22, 1.17, and 1.43. The all-cause mortality incidence rate was the highest in BMI<25 in men (2.71 per 1000 person-years), but BMI>30 in women (1.43 per 1000 person-years). Also, the all-cause mortality incidence rate twas he lowest among overweight subjects in both sexes. Overall, all-cause mortality was higher in men compared to women in all categories.

The BMI-specific WC threshold based on incident CVD and all-cause mortality were demonstrated in Tables 4. The WC cut-point predicting incident CVD in normal weight men (BMI<25) was 82cm, while the higher cut-point (88cm) was determined based on all-cause mortality. The cut-points predicting incident CVD and all-cause mortality were similarly 95cm in 25>BMI>30 and 103cm in BMI>30. In women, WC threshold predicting incident CVD and all-cause mortality were almost the same in the normal weight and overweight group (82 and 83cm in BMI<25 groups; 89 and 90cm in 25>BMI>30; and 100 and 99 in BMI>30, for incident CVD and all-cause mortality; respectively). Sensitivity and specificity for different WC regarding incident CVD and all-cause mortality were presented in Supplementary Tables 1 and 2, respectively.

The Kaplan-Meier survival curves compared the probability of survival/incident between the ones below and above defined cut-points based on incident CVD and all-cause mortality (Figure 1). The C-index was ranged from 0.569 to 0.677, and there were no significant differences between C-indices for cut-points based on incident CVD and all-cause mortality. Also, the C-indices were slightly higher in women than men, although only in overweight group the difference was significant, as presented in Tables 4. After sensitivity analysis by putting away incidents happened in the first two years of the follow-up, the same results were yielded.

This large prospective cohort study intended to evaluate WC threshold specific for each BMI group, predicting future CVD and all-cause mortality. In men with BMI >25, the WC threshold was 82cm based on incident CVD and 88cm based on all-cause mortality as an outcome variable. The WC cut-offs were 95 and 103cm in men with 25< BMI < 30 and BMI >30, respectively, for CVD incidence and all-cause mortality. In women, the WC cut-offs were 82 and 83; 89 and 90; and 100 and 99cm for BMI <25, 25< BMI <30 and BMI >30 groups based on CVD incidence and all-cause mortality, respectively.

Although the correlation of BMI and WC with CVD risk factors had been well established in many previous studies (32–34) it is not yet well understood how BMI and WC are related to endpoint variables like incident CVD, all-cause, and CVD-related mortality. Studies demonstrated that in certain groups, like patients with chronic diseases of patients with established coronary artery diseases, a U-shaped correlation between BMI and mortality is present, in which overweight, and mildly obese patients have lower mortality and patients with lower BMI or too high BMI values, experience higher incidents of mortality and CVD events, (35–38) a phenomenon called obesity paradox (39). In the study of Adegbija et al. (36), the risk of all-cause mortality was decreased by 9% with each standard deviation increase in BMI, while it increased by 17% with each standard deviation increase in WC. In another cohort study on the Spanish elderly,(38) mortality was 15% lower in the upper quartile of BMI than the lower quartile. After adjustment for WC, the negative correlation of BMI and mortality was stronger, and it was 37% lower in the upper quartile than the lower quartile of BMI.

In contrast, while WC was not associated with mortality before adjustment for BMI, the increase in mortality rate was observed in the higher WC quartile than the lower quartile after adjustment for BMI. Also, the same results were observed in a study on patients’ mortality after myocardial infarction (MI),(37) in which the hazard ratio per increase in standard deviation for mortality was 0.64 for BMI and 1.55 for WC. As observed in previous studies, WC seems to be a better variable to predict mortality or CVD events than BMI.

In our study, the CVD incident rate increased from normal weight to overweight, and from overweight to obesity group, in both men (CVD incidence rate of 3.1, 4.3, 4.5 per 1,000 in normal weight, overweight and obese males, respectively) and women (CVD incidence rate of 1.1, 2.1, 2.6 per 1,000 in normal weight, overweight and obese females, respectively). All-cause mortality was the highest in BMI <25 in men (incidence rate 2.71 per 1,000). All-cause mortality in obese men was also higher among overweight subjects (2.16 vs 2.07 per 1,000). In women, while the highest all-cause mortality was seen among obesity group (1.43 per 1,000), it was higher in BMI <25 (1.22 per 1,000) than in 25< BMI <30 (1.17 per 1,000).

The combination use of BMI and WC can be a more accurate approach in the prediction of mortality, as seen in previous studies (40,41). In a study on more than 23 million Korean population, there was a linear association between WC and all-cause mortality among all BMI categories (40). It is well established that within any given BMI, WC is varied considerably, in which the health risks are correlated with WC. In a pooled analysis of 11 studies on 650,000 subjects, mortality was increased by WC within each BMI category (11). Although, when BMI was adjusted with WC, the results were not the same, and mortality was lower in higher BMI (42). The association of WC with incident CVD and CVD mortality has also been established in several studies (43–45). In a prospective cohort study, higher nonfatal and fatal CVD incidents were reported to be related to higher WC (45). In another cohort study on more than 58,000 elderly subjects, large WC was associated with a higher relative risk of CVD mortality among each BMI group (44).

The most common WC threshold being used is the sex-specific WC cut-off points in National Institute of Health (NIH) guidelines that were originally developed by Lean and colleagues (18) which is 102cm for men and 88cm for women corresponding to BMI 30 kg/m². In recent years many studies suggested different WC cut-off points based on the prediction of CVD risk factors and incidence of metabolic syndrome (19–21). These cut-off values that was based on prediction of metabolic syndrome and cardiometabolic alterations were ranged from 85cm to 95cm in men and 80cm to 90cm in women in different ethnicities. Few studies evaluated the WC threshold based on CVD outcomes (22,23). In a study by Talaei et al. (22), the optimal WC cut-off points regarding CVD events were 99cm for men and 103cm for women. The other study suggested WC threshold of 94.5cm as the optimal threshold predicting CVD events (23). This study was performed by Hadaegh et al. in 2009, also in the framework of TLGS with shorter follow up time utilizing different analysis methods and without considering BMI categories. The cut-offs suggested in the two studies mentioned above were more in line with our suggested cut-offs and higher, in contrast to the studies in which the endpoint variables were metabolic syndrome or cardiovascular risk factors.

The study of Talaei and colleagues (22), along with the aforementioned cut-offs (99cm for men and 103cm for women), suggested other cut-points that are 93cm and 97cm for men and women, respectively as the first cut-offs had low sensitivity. There is a trade-off between sensitivity and specificity, in which in order to reach higher sensitivity, specificity should be sacrificed and vice versa. The optimal cut-points in our study were defined as the Youden index reaching the maximum level. But it should be considered that for WC values which are often used as a screening tool, sensitivity is of greater importance. In the study of Lee et al. (46), the BMI-specific WC thresholds were reported regarding cardiovascular risk factor prediction for values with at least 80% sensitivity. The suggested thresholds were 80 and 89cm for normal weight and overweight men and 78 and 94cm for women, respectively, which except in overweight women, are lower values than our suggested thresholds. In our study, the sensitivity ranged from 31.7 to 100%, and the specificity ranged from 38.2 to 78.2%. The lowest sensitivity values were observed in men with BMI <25 regarding CVD mortality and all-cause mortality with the sensitivity of 32.6 and 31.7%, respectively. These values, 88cm for both, are remarkably higher than WC cut-off in the same group regarding CVD incidence that is 82cm. The other WC threshold in the aforementioned group regarding CVD mortality and all-cause mortality, considering values with sensitivity higher than 60%, would be 82 and 80cm, respectively.

According to the results of our study, the WC threshold regarding incident CVD, CVD mortality, and all-cause mortality were 82 to 88cm for normal weight, 95, and 103cm for overweight and obese participants in men. The corresponding values in women were 82 to 83, 89 to 90, and 99 to 100cm in women in normal weight, overweight, and obesity group, respectively. Few other studies evaluated BMI-specific WC cut points.(24,47) In the study of Staiano and colleagues,(47) the evaluated WC cut-offs regarding cardiometabolic risk factors prediction were 82, 95, 107, and 120cm in white men; and 72, 87, 97, and 111cm in women in normal weight, overweight, obesity I and obesity II group, respectively. The evaluated values are almost the same as the results of our study, while in women, the values are lower compared to our study. In the other study, the WC threshold was evaluated in different ethnicities to predict a high risk of coronary events. The WC cut-offs were 82-89, 95-99, 106-110 and 109-125cm in men; and 79-81, 90-93, 100-104 and 112-116cm in women in normal weight, overweight, obesity I and obesity II groups, respectively (24). Also, these results are close to the results of our study.

This study has several points of strength. The long median follow-up time, prospective study design, using incident CVD and events as endpoint variables, and using subjective data instead of self-report data, can be mentioned. Regarding limitations of the study, the data were obtained from the middle-east Caucasian residents of a metropolitan city of Iran, and it is not nationally representative. Different methods of WC measurement have been established. Although it is unlikely that the method of WC measurement affects the results (13), it should be considered in the comparison of the results of different studies. WC was measured at umbilical level in our study.

In conclusion, the results of this study suggested a BMI-specific WC threshold based on incident CVD and mortality, which can give a clue to future studies to define a more accurate cut-off for WC as a screening tool to better identify individuals with a high risk of developing CVD and to take effective actions into account to modify risk factors.

Ethics approval and consent to participate: Informed consent was obtained from all participants. All methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki). This study was approved by the Ethics Committee of the Institute of Endocrinology and Metabolism of Shahid Beheshti University of Medical Sciences

Consent for publication Not Applicable.

Avalibility of data and materials: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interest: The authors declare that they have no financial or non-financial competing interests.

Funding: None

Author Contributions.

MB, AS, designed the study and prepared the manuscript and approved the final manuscript as submitted. MM: analyzed and interpreted the data. MV, FA and SG supervised the project, drafted the initial manuscript, and approved the final manuscript as submitted. .FH: conceptualized and designed the study, interpreted the data and critically revised the manuscript and approved the final manuscript as submitted. All authors reviewed and approved the final draft of the manuscript.

Acknowledgments.

We express our appreciation to the participants of the study for their enthusiastic support and to the staff of the involved TLGS unite for their valuable help.

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Table 1. Baseline characteristics of Men participants

	BMI<25 N=1264 (37.8%)	25<BMI<30 N=1541 (46.1%)	BMI>30 N=536 (16.1%)	Total N=3344	P-Value
Age (year)	47.4 ± 13.7	47.2 ± 12.4	46.8 ± 12.3	47.2 ± 12.9	0.559
Weight (kg)	65.0 ± 6.9	78.2 ± 7.2	92.5 ± 10.1	75.5 ± 12.2	< 0.001
BMI (kg/m²)	22.6 ± 1.7	27.2 ± 1.4	32.4 ± 2.6	26.3 ± 3.8	< 0.001
WC (cm)	81.8 ±6.7	93.8 ± 6.1	105.0 ± 7.7	91.1 ± 10.5	< 0.001
Family history of CVD, n(%)	146 (11.6)	211 (13.7)	102 (19.0)	459 (13.8)	< 0.001
Smoking, n(%)	435 (34.6)	495 (25.7)	129 (24.0)	959 (28.8)	< 0.001
SBP (mmHg)	116.4 ± 17.2	122.8 ± 18.2	127.3 ± 19.8	121.1 ± 18.6	< 0.001
DBP (mmHg)	74.8 ± 10.5	79.7 ± 10.8	82.9 ± 10.9	78.4 ±11.1	< 0.001
HTN, n(%)	178 (14.3)	379 (24.8)	173 (32.4)	730 (22.1)	< 0.001
FPS (mg/dL)	95.4 ±27.5	100.2 ± 30.1	105.2 ± 33.4	99.2 ± 29.9	< 0.001
2hBG(mg/dL)	103.8 ± 46.6	123.4 ± 64.9	131.8 ± 65.3	117.4 ± 59.8	< 0.001
DM, n(%)	180 (15.1)	379 (26.0)	184 (35.4)	743 (23.5)	< 0.001
TC (mg/dL)	197.1 ± 40.4	210.7 ± 42.7	215.8 ± 40.1	206.4 ± 42.1	< 0.001
HDL-C (mg/dL)	39.4 ± 9.9	36.6 ± 8.8	36.1 ± 8.9	36.1 ±8.9	< 0.001
LDL-C (mg/dL)	127.6 ± 34.7	134.1 ± 36.2	137.9 ±35.6	132.2 ± 35.8	< 0.001
TG (mg/dL)‡	129.0 (89.8-183.0)	178.5 (130.0-253.8)	202.5 (149.0-267.8)	163.0 (113.0-233.0)	< 0.001
BMI, body mass index; 2hPG, 2 hour post-prandial blood sugar; TC, total cholesterol; CVD, cardiovascular disease; DBP, diastolic blood pressure; DM, diabetes mellitus; HDL-C, high-density lipoprotein cholesterol; HTN, hypertension; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; TG, triglyceride. Data are given as the mean (SD) or median (IQ 25–75) unless otherwise indicated (‡).

Table 2. Baseline characteristics of Women participants

	BMI<25 N=919 (22.6%)	25<BMI<30 N=1708 (42.0%)	BMI>30 N=1441 (35.4%)	Total N=4068	P-Value
Age (year)	43.2 ± 12.3	46.0 ± 11.5	47.3 ± 10.6	45.8 ± 11.4	<0.001
Weight (kg)	56.2 ± 5.8	66.9 ± 5.7	80.6 ± 9.8	69.4 ± 11.9	<0.001
BMI (kg/m²)	22.9 ± 1.6	27.5 ± 1.4	33.5 ± 3.2	28.6 ± 4.6	<0.001
WC (cm)	78.2 ± 7.3	88.7 ± 7.8	100.9 ± 9.0	90.7 ± 11.9	<0.001
Family history of CVD, n (%)	151 (16.5)	301 (17.7)	276 (19.2)	728 (17.9)	0.222
Smoking, n (%)	39 (4.3)	64 (3.8)	51 (3.5)	154 (3.8)	0.670
SBP (mmHg)	113.7 ± 17.9	120.3 ± 19.6	126.3 ± 20.2	120.9 ± 20.0	<0.001
DBP (mmHg)	73.9 ± 9.8	78.1 ± 10.0	82.6 ± 10.8	78.8 ± 10.8	<0.001
HTN, n (%)	132 (14.5)	390 (22.9)	539 (37.7)	1061 (26.2)	<0.001
FPS (mg/dL)	95.3 ± 33.5	100.6 ± 36.6	104.2 ± 36.4	100.7 ± 36.0	<0.001
2hBG(mg/dL)	109.9 ± 43.8	125.1 ± 56.2	135.3 ± 58.0	125.2 ± 55.1	<0.001
DM, n (%)	157 (18.0)	456 (27.7)	516 (37.2)	1129 (28.9)	<0.001
TC (mg/dL)	203.4 ± 42.9	219.7 ± 47.1	226.0 ± 47.1	218.3 ± 46.9	<0.001
HDL-C (mg/dL)	46.9 ± 11.0	43.9 ± 11.3	43.0 ± 10.3	44.3 ± 11.0	<0.001
LDL-C (mg/dL)	130.4 ± 36.6	141.4 ± 39.0	144.1 ± 38.9	139.8 ± 38.8	<0.001
TG (mg/dL)‡	109.0 (80.0-158.0)	151.0 (105.0-213.0)	177.0 (127.0-235.0)	150.0 (103.0-212.0)	<0.001
BMI, body mass index; 2hPG, 2 hour post-prandial blood sugar; TC, total cholesterol; CVD, cardiovascular disease; DBP, diastolic blood pressure; DM, diabetes mellitus; HDL-C, high-density lipoprotein cholesterol; HTN, hypertension; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; TG, triglyceride. Data are given as the mean (SD) or median (IQ 25–75) unless otherwise indicated (‡).

Table 3. Incident cardiovascular disease (CVD) and all-cause mortality in BMI categories and hazard ratios per 1cm increase in WC within each BMI categories

	Men			Women
	BMI<25	25<BMI<30	BMI>30	BMI<25	25<BMI<30	BMI>30
CVD
No of person-year	6626515	8106047	2808150	5301946	9521589	7897815
No of CVD incident	206	335	126	60	196	207
Incidence rate (Per 1,000 person-years)	3.11 (2.7−3.6)	4.13 (3.71−4.60)	4.49 (3.8−5.4)	1.13 (0.9−1.5)	2.06 (1.8−2.4)	2.62 (2.3−3.0)
Hazard ratios (95%CI) (Per 1cm increase in WC)	1.054 (1.03−1.07)	1.041 (1.02−1.06)	1.035 (1.01−1.05)	1.081 (1.05−1.11)	1.068 (1.05−1.09)	1.041 (1.03−1.06)
All-cause mortality
No of person-year	6968967	8826047	3054811	5403171	9937393	8307184
No of CVD incident	189	183	66	66	117	119
Incidence rate (Per 1,000 person-years)	2.71 (2.3−3.1)	2.07 (1.79−2.40)	2.16 (1.70−2.75)	1.22 (0.9−1.5)	1.17 (0.9−1.4)	1.43 (1.2−1.7)
Hazard ratios (95%CI) (Per 1cm increase in WC)	1.047 (1.02−1.07)	1.034 (1.01−1.06)	1.029 (1.00−1.06)	1.056 (1.02−1.09)	1.123 (1.10−1.15)	1.068 (1.05−1.09)
BMI, body mass index; CI, confidence interval; CVD, cardiovascular disease; WC, waist circumference

Table 4.Waist circumference cut-points predicting cardiovascular disease and all-cause mortality

	Sex	BMI Category	Cut-point	Sensitivity	Specificity	Youden’s index	C-Index (95% CI)
CVD	Men	BMI<25	82	0.709	0.454	0.163	0.601 (0.56−0.64)
		25<BMI<30	95	0.607	0.521	0.128	0.573 (0.54−0.60)
		BMI>30	103	0.749	0.382	0.131	0.572 (0.52−0.62)
	Women	BMI<25	82	0.577	0.681	0.258	0.677 (0.60−0.75)
		25<BMI<30	89	0.791	0.476	0.267	0.653 (0.62−0.69)
		BMI>30	100	0.756	0.440	0.196	0.613 (0.57−0.65)
All-cause Mortality	Men	BMI<25	88	0.317	0.761	0.078	0.599 (0.56−-0.64)
		25<BMI<30	95	0.534	0.540	0.074	0.573 (0.54−0.60)
		BMI>30	103	0.780	0.391	0.171	0.569 (0.52−0.62)
	Women	BMI<25	83	0.551	0.710	0.261	0.677 (0.60−0.75)
		25<BMI<30	90	0.863	0.532	0.386	0.653 (0.62−0.69)
		BMI>30	99	0.932	0.407	0.339	0.613 (0.57−0.65)
	CVD; Cardio –vascular disease, BMI; body mass index.

No competing interests reported.

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BMI category-specific waist circumference thresholds based on cardiovascular disease outcomes and all-cause mortality: Tehran Lipid and Glucose Study (TLGS)

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