A total of 517 of 813 participants (63%) recruited at baseline completed the five-year follow-up assessment. The main reasons for not completing the study were lost-to-follow-up in which the participant’s contact information was no longer valid and refusal to participate due to lack of interest. Completers were older (p = 0.008), had a lower BMI (p = 0.005), waist circumference (p < 0.001), less likely to have HTGW (p < 0.001), be a current smoker (p < 0.001), be Aboriginal (p < 0.001), but more likely to have a higher education (p < 0.001) and a higher income (p < 0.001) than non-completers (Supplementary 1).
Table 1 outlines the baseline characteristics of the study participants by HTGW components. Significant differences were observed for ethnicity (p < 0.001), BMI (p < 0.001), total cholesterol (p < 0.001), HDL-C (p < 0.001), systolic blood pressure (p < 0.001) and smoking status (p < 0.001) by HTGW phenotype. The prevalence of current smokers was greater in the HTGW group. Baseline IMT and total area also varied significantly by HTGW whereas plaque presence did not.
Table 1
Baseline characteristics of the study population stratified by presence of HTGW components
Characteristic
|
Non-HTGW (Healthy)
(n = 312)
|
Elevated WC
(n = 254)
|
Elevated TG
(n = 91)
|
HTGW
(n = 156)
|
Significance
(p-value)
|
Age
|
46.9 ± 8.8
|
46.9 ± 8.5
|
46.9 ± 9.1
|
45.5 ± 8.8
|
0.36
|
Sex
|
|
|
|
|
|
Male
|
138 (44.2%)
|
137 (53.9%)
|
33 (36.3%)
|
84 (53.8%)
|
0.006
|
Ethnicity
|
|
|
|
|
< 0.001
|
Aboriginal
|
37 (11.9%)
|
89 (35.0%)
|
14 (15.4%)
|
47 (30.1%)
|
|
Chinese
|
113 (36.2%)
|
40 (15.7%)
|
42 (46.2%)
|
25 (16.0%)
|
|
European
|
88 (28.2%)
|
68 (26.8%)
|
7 (7.7%)
|
38 (24.4%)
|
|
South Asian
|
74 (23.7%)
|
57 (22.4%)
|
28 (30.8%)
|
46 (29.5%)
|
|
Family History of CVD Present (%)
|
149 (47.8%)
|
113 (44.5%)
|
43 (47.3%)
|
71 (45.5%)
|
0.88
|
Maximum Education
|
|
|
|
|
0.002
|
Less than High School
|
27 (8.7%)
|
40 (15.7%)
|
6 (6.6%)
|
23 (14.7%)
|
|
High School Graduate
|
62 (64.5%)
|
46 (18.1%)
|
29 (31.9%)
|
31 (19.9%)
|
|
Some Post-Secondary Education
|
35 (11.2%)
|
48 (18.9%)
|
10 (11.0%)
|
24 (15.4%)
|
|
Post-Secondary Degree/Diploma
|
133 (42.6%)
|
94 (37.0%)
|
39 (42.9%)
|
53 (34.0%)
|
|
Post Graduate Education
|
55 (17.6%)
|
25 (9.8%)
|
7 (7.7%)
|
24 (15.4%)
|
|
Annual Income Level
|
|
|
|
|
0.099
|
< $20,000
|
36 (11.5%)
|
36 (14.2%)
|
14 (15.4%)
|
24 (15.4%)
|
|
$20,000 - $30,000
|
40 (12.8%)
|
33 (13.0%)
|
11 (12.1%)
|
21 (13.5%)
|
|
$30,000 - $40,000
|
35 (11.2%)
|
40 (15.7%)
|
16 (17.6%)
|
29 (18.6%)
|
|
$40,000 - $50,000
|
40 (12.8%)
|
25 (9.8%)
|
9 (9.9%)
|
25 (16.0%)
|
|
$50,000 - $60,000
|
42 (13.5%)
|
17 (6.7%)
|
12 (13.2%)
|
12 (7.7%)
|
|
> $60,000
|
115 (36.9%)
|
95 (37.4%)
|
28 (30.8%)
|
44 (28.2%)
|
|
Smoking
|
|
|
|
|
< 0.001
|
Never Smoker
|
215 (68.9%)
|
140 (55.1%)
|
68 (74.7%)
|
79 (50.6%)
|
|
Former Smoker
|
77 (24.7%)
|
87 (34.3%)
|
15 (16.5%)
|
48 (30.8%)
|
|
Current Smoker
|
20 (6.4%)
|
27 (10.6%)
|
8 (8.8%)
|
29 (18.6%)
|
|
Body Mass Index (kg/m2)
|
24.0 ± 2.8
|
30.3 ± 4.0
|
25.1 ± 2.2
|
31.3 ± 4.4
|
< 0.001
|
Total Cholesterol (mmol/L)
|
5.09 ± 0.99
|
5.00 ± 0.89
|
5.73 ± 1.07
|
5.63 ± 0.91
|
< 0.001
|
HDL-C (mmol/L)
|
1.45 ± 0.36
|
1.26 ± 0.31
|
1.19 ± 0.35
|
1.08 ± 0.28
|
< 0.001
|
Systolic Blood Pressure (mm HG)*
|
112 [105, 120]
|
119 [111, 127]
|
115 [107, 124]
|
120 [114, 129]
|
< 0.001
|
Intima Media Thickness (mm)*
|
0.63 [0.58, 0.71]
|
0.67 [0.60, 0.76]
|
0.64 [0.59, 0.72]
|
0.67 [0.60, 0.75]
|
0.001
|
Total Area (mm2)*
|
14.62 [12.20, 21.05]
|
16.60 [13.10, 25.31]
|
15.47 [11.90, 24.36]
|
17.60 [13.50, 23.54]
|
0.01
|
Presence of Plaque
|
154 (49.4%)
|
133 (52.4%)
|
45 (49.5%)
|
96 (61.5%)
|
0.08
|
Categorical variables presented as n (%). Normally distributed continuous variables presented as mean ± SD. *Skewed continuous variables presented as median (25%, 75%). Completion differences in continuous and categorical variables were explored by ANOVA and Chi-square test, respectively. Elevated waist circumference (WC) was ≥ 85 cm in women and ≥ 90 cm in men. Elevated triglycerides (TG) were ≥ 1.5 mmol/L in women and ≥ 2 mmol/L in men. HTGW is the presence of both elevated WC and TG. CVD: cardiovascular disease; MET: metabolic equivalent; BMI: body mass index; HDL-C: high-density lipoprotein cholesterol; HTGW: hypertriglyceridemic waist; WC: waist circumference; TG: triglycerides. |
Presence of baseline HTGW phenotype was weakly, but positively correlated with five-year IMT (rpb =0.11, p = 0.02), total area (rpb =0.13, p = 0.00), and plaque presence (2.06 (1.13, 3.74), p = 0.02). Additionally, a significant inverse association was observed between the presence of elevated TG phenotype at baseline with the five-year total area (rpb =-0.11, p = 0.01) (Supplementary 2). However, this association was not significant when adjusting for sociodemographic and traditional risk factors in Table 2. When adjusting for sociodemographic factors (age, sex, ethnicity, income level, maximum education) and family history in model A, a statistically and clinically significant association was observed between the presence of HTGW phenotype with average IMT (0.08 [0.04, 0.11], p < 0.001), total area (0.20 [0.07, 0.33], p = 0.002), and plaque presence (OR = 2.17 [1.13, 4.19], p = 0.02) compared to the non-HTGW group (Table 2). Presence of elevated WC at baseline was also positively associated with five-year IMT outcome (0.05 [0.02, 0.09], p = 0.002) compared to the non-HTGW group. Upper limits of normal for average IMT and total area are roughly 0.9 mm and 18.3 mm2, respectively (16). When adjusting for traditional risk factors of atherosclerosis (BMI, smoking status, total cholesterol, HDL-C, and systolic blood pressure systolic blood pressure) and sociodemographic factors in model B, we found no significance between elevated WC, elevated TG, and HTGW phenotypes with indices of atherosclerosis, compared to the non-HTGW group. We also investigated the change in standardized β for the variables in each linear regression model (Supplementary 3) and found that compared to model A, HTGW phenotype was not significant in model B but total cholesterol and systolic blood pressure were significant. Total cholesterol and systolic blood pressure were associated with average IMT (std. β = 0.09, p = 0.03; std. β = 0.12, p = 0.003), total area (std. β = 0.19, p < 0.001; std. β = 0.12, p = 0.01), and plaque presence (OR = 1.52, p < 0.001; OR = 1.28, p = 0.05) in model B. Total cholesterol and systolic blood pressure may be largely mediating the association between elevated WC and HTGW phenotypes with IMT, the effect of HTGW with total area, and the effect of HTGW with plaque presence.
Table 2
The association of HTGW phenotype components with 5-year subclinical carotid artery atherosclerosis indices.
|
Intima Media Thicknessa
|
Total Areaa
|
Plaque Presenceb
|
Model A
|
β (95% CI)
|
p-value
|
β (95% CI)
|
p-value
|
OR (95% CI)
|
p-value
|
Non-HTGW
|
Reference
|
Reference
|
Reference
|
Reference
|
Reference
|
Reference
|
Elevated WC
|
0.05 (0.02, 0.09)
|
0.002
|
0.05 (-0.06, 0.16)
|
0.33
|
1.03 (0.62, 1.69)
|
0.92
|
Elevated TG
|
0.02 (-0.03, 0.07)
|
0.39
|
-0.02 (-0.17, 0.14)
|
0.85
|
0.78 (0.40, 1.50)
|
0.46
|
HTGW
|
0.08 (0.04, 0.11)
|
< 0.001
|
0.20 (0.07, 0.33)
|
0.002
|
2.17 (1.13, 4.19)
|
0.02
|
Model B
|
|
|
|
|
|
|
Non-HTGW
|
Reference
|
Reference
|
Reference
|
Reference
|
Reference
|
Reference
|
Elevated WC
|
0.02 (-0.02, 0.07)
|
0.24
|
0.02 (-0.11, 0.16)
|
0.76
|
0.81 (0.42, 1.56)
|
0.53
|
Elevated TG
|
0.00 (-0.05, 0.05)
|
0.94
|
-0.12 (-0.28, 0.04)
|
0.14
|
0.51 (0.24, 1.07)
|
0.08
|
HTGW
|
0.03 (-0.02, 0.08)
|
0.27
|
0.06 (-0.10, 0.22)
|
0.45
|
1.21 (0.53, 2.75)
|
0.66
|
Outcome variables are in ln(x) form; a multiple linear regression; b logistic regression; Model A adjusts for age, maximum education, sex, family history, ethnicity, and income level; Model B adjusts for all variables adjusted for in model A plus: BMI, smoking status, total cholesterol, HDL-C, systolic blood pressure; Elevated waist circumference (WC) was ≥ 85 cm in women and ≥ 90 cm in men; Elevated triglycerides (TG) were ≥ 1.5 mmol/L in women and ≥ 2 mmol/L in men; HTGW is the presence of both elevated WC and TG; BMI: body mass index; HDL-C: high-density lipoprotein cholesterol; HTGW: hypertriglyceridemic waist; WC: waist circumference; TG: triglycerides. |
From baseline to follow-up, IMT and total area increased significantly within all HGTW categories (Table 3). We observed no significant differences between HTGW categories for the increase in these variables (p = 0.99 for IMT; p = 0.35 for total area). Plaque presence increased significantly within all HTGW categories between baseline and follow-up with the exception of people who experienced HTGW reversal. We did not observe a significant difference between HTGW categories for the baseline to follow-up change in plaque presence (p = 0.06). Adjustments for sociodemographic and traditional risk factors did not change these findings (Supplementary 4 and 5).
Table 3
Comparing within- and between- HTGW group differences for atherosclerosis outcome measures without adjusting any covariates.
|
Without HTGW at Baseline and Follow-up (N = 376)
|
With HTGW at Baseline and Follow-up (N = 49)
|
Acquired HTGW
(N = 50)
|
Reversed HTGW
(N = 37)
|
Between-Group Differences
|
|
baseline
|
5yr
|
baseline
|
5yr
|
baseline
|
5yr
|
baseline
|
5yr
|
p-value
|
Intima Media Thickness (mm)
|
0.67 ± 0.12*
|
0.72 ± 0.14*
|
0.71 ± 0.12*
|
0.77 ± 0.14*
|
0.65 ± 0.09*
|
0.70 ± 0.11*
|
0.70 ± 0.13*
|
0.75 ± 0.16*
|
0.99
|
Total area (mm2)
|
21.35 ± 16.65*
|
27.82 ± 23.71*
|
25.64 ± 18.40*
|
35.25 ± 23.92*
|
17.75 ± 7.45*
|
24.71 ± 14.29*
|
22.15 ± 13.14*
|
30.54 ± 25.42*
|
0.35
|
Plaque presence
|
200 (53.2%)*
|
252 (67.0%)*
|
30 (61.2%)*
|
42 (85.7%)*
|
25 (50.0%)*
|
34 (68.0%)*
|
27 (73.0%)
|
27 (73.0%)
|
0.06
|
Categorical variables presented as n (%). Continuous variables presented as mean ± SD. Paired-samples t-test used to test within-group differences for continuous variables. McNemar tests used to test within-group differences for categorical variables. ANCOVA used to test between-group differences for continuous variables. For this test, the follow-up assessment was used as the outcome variable and the baseline variable was controlled for. Chi-square used to test between-group differences for categorical variables. To test between group variables, change in plaque presence was considered in four groups of no change absence of plaque, no change presence of plaque, acquired plaque, plaque reversed. * marks a significant within-group difference between baseline with 5 year at 0.01. Elevated waist circumference (WC) was ≥ 85 cm in women and ≥ 90 cm in men. Elevated triglycerides (TG) were ≥ 1.5 mmol/L in women and ≥ 2 mmol/L in men. HTGW is the presence of both elevated WC and TG. Acquired HTGW refers to those with no HTGW at baseline who tested positive in the follow-up assessment. HTGW reversed, inversely, refers to those with HTGW at baseline who tested negative in the follow-up assessment. |
Furthermore, the regression models A and B were run a second time for all atherosclerosis indices while controlling for the baseline reading of each index (Table 4). We observed no significant associations between any of the baseline HTGW phenotypes with any of the five-year indices of atherosclerosis when controlling for the baseline readings of each index.
Table 4
Association of HTGW phenotypes with 5-year subclinical atherosclerosis indices while adjusting for each baseline index.
|
Intima Media Thicknessa
|
Total Areaa
|
Plaque Presenceb
|
Model A
|
β (95% CI)
|
p-value
|
β (95% CI)
|
p-value
|
OR (95% CI)
|
p-value
|
Non-HTGW
|
Reference
|
Reference
|
Reference
|
Reference
|
Reference
|
Reference
|
Elevated WC
|
0.02 (0.00, 0.03)
|
0.10
|
0.05 (-0.03, 0.12)
|
0.22
|
1.34 (0.71, 2.52)
|
0.36
|
Elevated TG
|
0.02 (-0.01, 0.05)
|
0.14
|
-0.01 (-0.11, 0.09)
|
0.86
|
0.87 (0.38, 2.00)
|
0.74
|
HTGW
|
0.02 (-0.01, 0.04)
|
0.18
|
0.08 (0.00, 0.16)
|
0.06
|
2.04 (0.91, 4.58)
|
0.09
|
Model B
|
|
|
|
|
|
|
Non-HTGW
|
Reference
|
Reference
|
Reference
|
Reference
|
Reference
|
Reference
|
Elevated WC
|
0.01 (-0.01, 0.03)
|
0.36
|
0.02 (-0.07, 0.11)
|
0.68
|
1.33 (0.59, 2.99)
|
0.49
|
Elevated TG
|
0.02 (-0.01, 0.04)
|
0.30
|
-0.06 (-0.16, 0.05)
|
0.30
|
0.66 (0.26, 1.68)
|
0.38
|
HTGW
|
0.01 (-0.02, 0.04)
|
0.58
|
0.01 (-0.10, 0.12)
|
0.82
|
1.48 (0.53, 4.11)
|
0.46
|
Outcome variables are in ln(x) form; a multiple linear regression; b logistic regression; Model A adjusts for age, maximum education, sex, family history, ethnicity, and income level; Model B adjusts for all variables adjusted for in model A plus: BMI, smoking status, total cholesterol, HDL-C, systolic blood pressure; Elevated waist circumference (WC) was ≥ 85 cm in women and ≥ 90 cm in men; Elevated triglycerides (TG) were ≥ 1.5 mmol/L in women and ≥ 2 mmol/L in men; HTGW is the presence of both elevated WC and TG; BMI: body mass index; HDL-C: high-density lipoprotein cholesterol; HTGW: hypertriglyceridemic waist; WC: waist circumference; TG: triglycerides. |