Body circumferences have been proposed as potential anthropometric measures for the assessment of cardiometabolic risk as they are independently associated with insulin resistance and diabetes. The aim of this study was to validate neck and wrist circumference and waist-to-hip ratio as practical markers of metabolic dysfunction and atherosclerosis; 120 subjects who underwent coronary angiography and carotid Doppler ultrasound were enrolled in this cross-sectional study. Exclusion criteria were history of diabetes, acute myocardial infarction, body mass index (BMI) <18.5 or ≥45.0 kg/m 2 . Metabolic dysfunction was ascertained by the calculation of visceral adiposity index (VAI) and by diagnosis of metabolic syndrome (MS). Advanced atherosclerotic disease was defined as ≥70% coronary lumen and/or ≥50% carotid lumen stenosis. No association between body circumferences and VAI or MS was found in subjects with BMI <25 kg/m 2 . VAI was significantly related to waist-to-hip ratio (R 2 = 0.09, p = 0.008), neck (R 2 = 0.09, p = 0.007), and wrist circumferences (R 2 = 0.05, p = 0.041) in subjects with BMI ≥25 kg/m 2 . In overweight subjects, higher gender-specific tertiles of wrist circumference were independently associated with an increased risk of MS (odds ratio 2.57, 95% confidence interval 1.11 to 5.96, p = 0.028). VAI was independently associated with carotid intima-media thickness: β = 0.104, R 2 = 0.118, p = 0.003. Carotid intima-media thickness and MS, but not body circumferences, were associated with advanced atherosclerosis. In conclusion, these data indicate that anthropometric measurements, in particular wrist circumference, can be used as practical tools for assessment of metabolic risk in overweight-obese subjects but not as markers of advanced atherosclerosis.
Obesity, usually assessed by body mass index (BMI), is a well-known risk factor for metabolic and cardiovascular disease (CVD). However, more than the amount of adipose tissue, its function, and distribution play important roles in the development of CVD. Measurement of body circumferences is an easy way to evaluate adipose tissue distribution in daily clinical practice. In particular, waist circumference is acknowledged among the diagnostic criteria of metabolic syndrome (MS). Beyond waist, neck and wrist circumferences have been suggested as potential anthropometric measurements of cardiometabolic risk given their independent association with insulin resistance and diabetes. However, whether these measures are a proxy for deleterious adipose deposition and function and clinically significant CVD is still controversial. Visceral adiposity index (VAI) is a sex-specific index proposed as a surrogate marker of adipose tissue function because of its strong association with adiponectin levels and cardiovascular and cerebrovascular events. In this study, we aimed to validate body circumferences (neck, wrist, and waist-to-hip ratio [WHR]) as practical markers of metabolic dysfunction, as correlates to VAI and MS, and also atherosclerosis.
Methods
This cross-sectional study enrolled consecutive subjects who underwent elective diagnostic coronary angiography and carotid Doppler ultrasound at the Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, from September 2014 to January 2015. Patients with history of diabetes, BMI <18.5 or ≥45.0 kg/m 2 , and presenting with acute myocardial infarction with or without ST-elevation were excluded from the study.
Baseline demographic data, medical history, concomitant medications, and anthropometric parameters were collected by study personnel. Detailed information about data collection are reported as Supplementary Material .
Before coronary angiography patients underwent laboratory testing including complete blood count, fasting glucose levels, lipid profile, liver and renal panel, and high-sensitivity C-reactive protein. According to the World Health Organization criteria, normal weight was defined as BMI values ≥18.5 and <25 kg/m 2 and overweight/obesity was defined as BMI values ≥25 kg/m 2 . MS was defined according to the 2005 International Diabetes Federation criteria. VAI was estimated using gender-specific formulas ( Supplementary Material ).
In addition to the assessment of angiographic coronary artery disease, all patients underwent a Doppler ultrasound of the carotid district with measurement of the common carotid intima-media thickness (cIMT). Experienced cardiologists reported the mean value of 3 repeated measurements of the cIMT 1 cm distal to the bulb. Advanced atherosclerosis was defined as ≥70% lumen stenosis of any coronary vessel requiring intervention or as ≥50% lumen stenosis of any carotid artery.
The study was performed in accordance with the Declaration of Helsinki, and the protocol was approved by the institution’s ethics committee, with all patients giving written informed consent.
Values are expressed as mean ± SD or median (interquartile range [IQR]) for continuous variables and as proportions for categorical variables (%). Shapiro-Wilk normality test was used to assess the normality of continuous variables distributions (variables with Shapiro-Wilk statistic <0.9, p values <0.05 were considered non-normally distributed). Comparisons between groups were done using the Student’s t test, Kruskal-Wallis, chi-square, and Fisher’s exact test depending on distribution. Adjusted associations were tested by linear or logistic regression. Variables that showed a p value of <0.1 in 2-way analysis were tested in the model for significance with the main effect and outcome variable. Nonparametric variables were natural log-transformed before testing in the model. A subgroup analysis was performed by subdividing the study population into 2 groups based on a BMI cutoff of 25 kg/m 2 . Two-tailed p value <0.05 was considered statistically significant. All statistical analyses were performed using Stata/IC 12.1 software (StataCorp, College Station, Texas).
Results
A total of 120 subjects (87 men and 33 women) were included in the study. The leading indications for diagnostic coronary angiography were routine preoperative evaluation in candidates for cardiac or vascular surgery, symptoms or noninvasive testing suggestive of myocardial ischemia. 69.4% (n = 83) of patients had at least 2 major cardiovascular risk factors (hypertension, dyslipidemia, current smoking, or family history of CVD) and 70.9% (n = 85) met the criteria of MS. Table 1 summarizes baseline features of the study population. Mean age was 68.3 ± 9.8 years. As expected, men showed higher values of WHR and wrist and neck circumferences compared with women (p <0.001 for all comparisons).
| Variable | Overall (n=120) | Males (n=87) | Females (n=33) | p-value (males vs. females) |
|---|---|---|---|---|
| Age (years) | 68.3 ± 9.8 | 67.8 ± 9.5 | 69.6 ±10.6 | 0.519 |
| Body Mass Index (kg/m 2 ) | 27.2 ± 3.7 | 27.4 ± 3.8 | 26.8 ± 3.7 | 0.437 |
| Waist to hip ratio | 0.97 ± 0.07 | 1.00 ± 0.06 | 0.91 ± 0.07 | <0.001 |
| Wrist Circumference (cm) | 17.1 ± 1.4 | 17.6 ± 1.0 | 15.8 ± 1.4 | <0.001 |
| Neck Circumference (cm) | 39.1 ± 3.8 | 40.7 ± 2.9 | 35.1 ± 2.6 | <0.001 |
| Hypertension | 78.3% | 79.3% | 75.8% | 0.673 |
| Fasting plasma glucose (mg/dl) | 97.0 ± 25.9 | 97.9 ± 29.4 | 94.6 ± 13.4 | 0.941 |
| Total cholesterol (mg/dl) | 166.5 ± 42.8 | 165.1 ± 40.2 | 170.5 ± 50.1 | 0.829 |
| LDL cholesterol (mg/dl) | 102.0 ± 35.6 | 102.5 ± 32.4 | 100.7 ± 43.9 | 0.319 |
| HDL cholesterol (mg/dl) | 47.2 ± 15.1 | 43.7 ± 13.4 | 57.2 ± 15.5 | <0.001 |
| Triglycerides (mg/dl) | 144.4 ± 89.7 | 154.7 ± 93.1 | 115.8 ± 73.4 | 0.008 |
| C-Reactive Protein (mg/l) | 3.72 ± 8.36 | 4.3 ± 9.5 | 2.0 ± 3.1 | 0.316 |
| Current smoking | 25.0% | 23.0% | 30.3% | 0.409 |
| Family history of CV disease | 23.3% | 19.5% | 33.3% | 0.111 |
| Metabolic syndrome | 70.9% | 71.4% | 69.7% | 0.853 |
| Visceral Adiposity Index | 2.44 ± 2.10 | 2.55 ± 2.12 | 2.16 ± 2.04 | 0.182 |
| carotid Intima-Media Thickness (mm) | 1.08 ± 0.30 | 1.12 ± 0.33 | 0.99 ± 0.19 | 0.016 |
| Statin therapy | 64.4% | 65.1% | 62.5% | 0.792 |
At the bivariate analysis in the whole population, VAI was significantly associated with WHR (R 2 = 0.13, p <0.001), wrist circumference (R 2 = 0.05, p =0.022), and neck circumference (R 2 = 0.12, p <0.001). These associations remained significant after controlling for age (WHR: adjusted R 2 (adj R 2 ) = 0.15, p <0.001; wrist: adj R 2 = 0.05, p = 0.036; neck: adj R 2 = 0.14, p <0.001). However, when BMI was introduced in the multivariate model, only the association between VAI and WHR remained significant (adj R 2 = 0.17, p = 0.003). The three circumferences were higher in those with MS compared with those without (gender-adjusted p-values: <0.01).
When the population was stratified by BMI categories, no association between body circumferences and VAI nor MS was found in subjects with BMI <25 kg/m 2 (n = 31). VAI was significantly associated with WHR and neck and wrist circumferences in subjects with BMI ≥25 kg/m 2 (n = 89; Figure 1 ). In this latter subgroup, VAI was not associated with age, gender, BMI, statin use, and total or LDL cholesterol levels ( Supplementary Figure 1 ).
Overweight/obese subjects with MS showed higher values of wrist and neck circumferences and WHR than those without MS. However, only the difference in wrist circumference remained significant after adjustment (BMI, gender, and age; adjusted p value = 0.042). Accordingly, higher gender-specific tertiles of wrist circumference were independently associated with an increased risk of MS in those with BMI ≥25 kg/m 2 but not of WHR or neck circumference ( Figure 2 ; Supplementary Table 1 ).
Advanced atherosclerotic disease was diagnosed in 73.3% (n = 88) of subjects enrolled; 64.2% (n = 77) of patients had significant coronary artery disease and 32.4% (n = 39) had significant carotid atherosclerosis. Mean cIMT was higher in men than in women. Regression analysis showed significant associations between cIMT and VAI (R 2 = 0.078, p = 0.007) and between cIMT and the triglycerides/high-density lipoprotein ratio (R 2 = 0.058, p = 0.019). These associations remained significant after adjustment for age, gender, and statin use ( Supplementary Table 2 ). After adjusting for gender, WHR, neck circumference, and wrist circumference were not associated with cIMT (p = 0.13 for WHR; p = 0.15 for neck circumference; p = 0.84 for wrist circumference).
Subjects with advanced atherosclerosis in at least 1 site (coronary and/or carotid) were more likely to be men, older, and affected by hypertension and MS than subjects without advanced atherosclerosis ( Table 2 ). The significant difference found in total and LDL cholesterol levels disappeared after adjustment for statin therapy. Table 3 summarizes the results of the logistic regression models for the association with advanced atherosclerosis in our cohort. Results indicate that cIMT and the presence of MS are associated with an increased rate of advanced atherosclerosis, independent of age and gender. In our cohort, VAI was not significantly associated with the diagnosis of advanced atherosclerosis. As well, neither BMI nor any body circumference measure or their gender-specific tertiles were independently associated with either the angiographic or ultrasonographic diagnosis of advanced atherosclerosis.
| Variable | Advanced atherosclerosis | p-value | |
|---|---|---|---|
| No (n=32) | Yes (n=88) | ||
| Gender | |||
| Men | 56.3% | 78.4% | |
| Women | 43.7% | 21.6% | 0.016 |
| Age (years) | 67.5 [58.0-72.5] | 71.5 [64.0-76.0] | 0.030 |
| Body Mass Index (kg/m 2 ) | 26.6 ± 3.7 | 27.4 ± 3.7 | 0.296 |
| Waist to hip ratio | |||
| Men | 0.99 ± 0.07 | 1.0 ± 0.05 | 0.429 |
| Women | 0.90 ± 0.08 | 0.92 ± 0.07 | 0.648 |
| Wrist Circumference (cm) | |||
| Men | 17.8 [17.1-18.4] | 17.7 [17.0-18.4] | 0.712 |
| Women | 16.0 [14.5-16.3] | 16.0 [14.5-17.1] | 0.264 |
| Neck Circumference (cm) | |||
| Men | 41.3 ± 3.5 | 40.5 ± 2.8 | 0.287 |
| Women | 34.2 ± 2.6 | 35.7 ± 2.5 | 0.106 |
| Hypertension | 62.5% | 84.1% | 0.011 |
| Fasting plasma glucose (mg/dl) | 91.5 [83.0-102.5] | 93.0 [85.0-103.0] | 0.383 |
| Total cholesterol (mg/dl) | 180.5 [161.0-228.0] | 154.5 [134.0-181.0] | <0.001 ∗ |
| LDL cholesterol (mg/dl) | 115.5 [98.0-156.0] | 91.5 [74.0-109.0] | <0.001 ∗ |
| HDL cholesterol (mg/dl) | |||
| Men | 44.0 [40.0-55.0] | 40.0 [33.0-50.0] | 0.268 |
| Women | 62.0 [51.0-71.0] | 52.0 [42.0-60.0] | 0.280 |
| Triglycerides (mg/dl) | 106.0 [67.5-154.0] | 110.5 [87.0-180.0] | 0.353 |
| C-Reactive Protein (mg/l) | 0.0 [0.0-3.9] | 1.3 [0.0-4.0] | 0.659 |
| Current smoking | 28.1% | 23.9% | 0.634 |
| Family history of CV disease | 34.4% | 19.3% | 0.085 |
| Metabolic Syndrome | 53.1% | 77.6% | 0.009 |
| Visceral Adiposity Index | 1.7 [1.0-2.2] | 1.9 [1.3-3.3] | 0.183 |
| Carotid Intima-Media Thickness (mm) | |||
| Men | 0.90 ± 0.38 | 1.17 ± 0.29 | 0.008 |
| Women | 0.87 ± 0.17 | 1.06 ± 0.16 | 0.005 |
| Statin Therapy | 25.0% | 79.1% | <0.001 |
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