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Basic characteristics of the study population are summarized in Table [1] A total of 1455 patients were enrolled in the analyses. Among these, 561 (38.6%) patients had been determined to have MetS, while the remaining 894 patients did not have MetS. According to the presence of metabolic components (overweight/obesity, hypertension, hypertriglyc eridemia and/or hypo HDL cholesterolemia, hyperglycemia), we found only 82 patients (5.6%) who were free of any metabolic disorders.
Patients with MetS were older than those without (56.6 ± 9.9 vs. 54.2 ± 11.7 years, P < 0.001) and 64.7% and 56.6% of patients with and without MetS, respectively, were men (P = 0.002). Additionally, the rates of the presence of each MetS risk component, in turn, were hypo HDL cholesterolemia (58.0%), hypertension (53.7%), overweight/obesity (52.8%), hypertriglyceridemia (42.0%), and hyperglycemia (25.0%) in the total population; and hypertension (89.7%), overweight/obesity (86.3%), hypo HDL cholesterolemia (73.4%), hypertriglyceridemia (53.5%), and hyperglycemia (53.5%) in patients with MetS.
Characteristics All Patients (n = 1455) With MetS (n = 561) Without MetS ( n = 894) P-value Age (years) 55.1 ± 11.1 56.6 ± 9.9 54.2 ± 11.7 < 0.001 Gender, men% (n) 59.7 (869) 64.7 (363) 56.6 (506) 0.002 Overweight/obesity, % (n) 52.8 (769) 86.3 (484) 31.9 (285) < 0.001 Hypertension, % (n) 53.7 (781) 89.7 (503) 31.1 (278) < 0.001 Hypertriglyceridemia, % (n) 42.0 (610) 53.5 (300) 34.7 (310) < 0.001 HypoHDL cholesterolemia, % (n) 58.0 (844) 73.4 (412) 48.3 (432) < 0.001 Hyperglycemia, % (n) 25.0 (364) 53.5 (300) 7.2 (64) < 0.001 BMI (kg/m2) 25.4 ± 3.5 27.5 ± 3.1 24.1 ± 3.0 < 0.001 SBP (mmHg) 129 ± 17 135±17 125±16 < 0.001 DBP (mmHg) 80 ± 11 85 ± 12 78 ± 10 < 0.001 TG (mmol/L) 1.6 (1.1-2.2) 1.9 (1.4-2.6) 1.4 (1.0-2.0) < 0.001 TC (mmol/L) 4.9 ± 1.1 5.0 ± 1.1 4.9 ± 1.1 0.112 HDL-C (mmol/L) 1.1 ± 0.3 1.0 ± 0.3 1.2 ± 0.4 < 0.001 LDL-C (mmol/L) 3.2 ± 1.0 3.3 ± 0.9 3.2 ± 1.0 0.006 Non-HDL-C (mmol/L) 3.8 ± 1.0 3.9 ± 1.0 3.7 ± 1.0 < 0.001 apoA1 (g/L) 1.4 ± 0.3 1.3 ± 0.3 1.4 ± 0.3 < 0.001 apoB (g/L) 1.1 ± 0.3 1.1 ± 0.3 1.0 ± 0.3 < 0.001 Glucose (mmol/L) 5.6 ± 1.6 6.2 ± 2.1 5.2 ± 1.0 < 0.001 HbA1C (%) 6.0 ± 1.0 6.4 ± 1.2 5.7 ± 0.7 < 0.001 hs-CRP (mg/L) 1.2 (0.6 - 2.6) 1.7 (0.8 - 3.4) 1.1 (0.5 - 2.2) < 0.001 WBC count (×109/L) 6.25 ± 1.68 6.48 ± 1.68 6.11 ± 1.67 < 0.001 apoCIII (μg/mL) 86.8 (64.0 - 121.8) 95.1 (73.1 - 131.4) 81.7 (58.6 - 112.4) < 0.001 Note. Data shown are mean ± SD, median (Q1-Q3 quartiles), or % (n). The bold values indicate statistical significance and are bolded to improve the readability of the table. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; Non-HDL-C, non-high density lipoprotein cholesterol; apo, apolipoprotein; HbA1C, hemoglobin A1C; hs-CRP, high sensitivity C-reactive protein; WBC, white blood cell. Table 1. Baseline Characteristics in Patients with or without MetS
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Patients with MetS showed higher levels of apoCIII than those without [apoCIII 95.1 (73.1-131.4) vs. 81.7 (58.6-112.4) μg/mL, P < 0.001] (Table 1). As shown in Figure 1: according to the number of MetS risk components (overweight/obesity, hyperglycemia, hypo HDL cholesterolemia and/or hypertriglyceridemia, hypertension), patients were divided into five groups: patients with 0 risk components (n = 82), 1 component (n = 355), 2 components (n = 457), 3 components (n = 412) and 4 components (n = 149). We found that apoCIII levels increased with the number of MetS risk components [60.0 (42.9-78.2) vs. 76.6 (57.7-102.2) vs. 87.6 (63.8-125.9) vs. 91.2 (71.1-125.6) vs. 115.4 (82.2-144.9) μg/mL, P for trend < 0.001]. The logistic regression analyses showed that compared to patients with 0 risk components of MetS, the ORs (95% CIs) of apoCIII levels for patients with 1: 2: 3: and 4 components were 1.016 (1.003-1.028), 1.022 (1.010-1.035), 1.024 (1.012-1.037), and 1.030 (1.017-1.042), respectively (Table 2).
Number of Mets Factors apoCIII (μg/mL) hs-CRP (mg/mL) WBC (×109/L) OR (95% CI) P-value OR (95% CI) P-value OR (95% CI) P-value 0 1 (reference) - 1 (reference) - 1 (reference) - 1 1.016 (1.003-1.028) 0.014 1.185 (1.023-1.372) 0.023 1.054 (0.989-1.159) 0.082 2 1.022 (1.010-1.035) < 0.001 1.207 (1.045-1.395) 0.011 1.157 (1.001-1.314) 0.041 3 1.024 (1.012-1.037) < 0.001 1.299 (1.126-1.501) < 0.001 1.243 (1.055-1.465) 0.009 4 1.030 (1.017-1.042) < 0.001 1.350 (1.164-1.566) < 0.001 1.302 (1.088-1.558) 0.004 Note. The bold values indicate statistical significance and are bolded to improve the readability of the table. Table 2. The Regression Analysis Regarding the Association of apoCIII, hs-CRP, and WBC with Number of MetS Factors
Figure 1. The associations of plasma apoCIII and inflammatory markers with the number of MetS risk components. Both levels of apoCIII (A) and inflammatory makers including hs-CRP (B), and WBC (C) increased with the number of MetS components (all P for trend < 0.001).
We additionally divided the patients according to the quartiles of apoCIII values to examine the presence of MetS in each metabolic disorder. As shown in Table 3: the prevalence of MetS rose in each MetS risk component as the levels of apoCIII increased (all P < 0.05). For example, in patients with overweight/obesity, patients who had higher apoCIII levels experienced a higher prevalence of MetS (Q1 vs. Q2 vs. Q3 vs. Q4: 53.8% vs. 59.4% vs. 66.0% vs. 70.7%, respectively, P for trend = 0.008). The same findings were also observed for apoCIII in patients with hypertension (48.9% vs. 58.2% vs. 71.5% vs. 75.7%, P for trend < 0.001), hypertriglyceridemia (17.7% vs. 37.5 vs. 51.6 vs. 55.4%, P for trend < 0.001), hypo HDL cholesterolemia (44.0% vs. 44.1% vs. 49.1% vs. 57.7%, P for trend = 0.034) and hyperglycemia (70.8% vs. 78.2% vs. 83.7% vs. 91.2%, P for trend = 0.01).
Item Q1 Q2 Q3 Q4 P for Trend Total (N) 363 364 364 364 MetS, % (n) 27.8 (101) 36.3 (132) 42.3 (154) 47.8 (174) < 0.001 Overweight/obese (N) 173 187 194 215 MetS, % (n) 53.8 (93) 59.4 (111) 66.0 (128) 70.7 (152) 0.008 Hypertension (N) 176 184 207 214 MetS, % (n) 48.9 (86) 58.2 (107) 71.5 (148) 75.7 (162) < 0.001 Hypertriglyceridemia (N) 24 120 186 280 MetS, % (n) 17.7 (4) 37.5 (45) 51.6 (96) 55.4 (155) < 0.001 Hypo HDL cholesterolemia (N) 193 211 218 222 MetS, % (n) 44.0 (85) 44.1 (93) 49.1 (106) 57.7 (128) 0.034 Hyperglycemia (N) 65 87 98 114 MetS, % (n) 70.8 (46) 78.2 (68) 83.7 (82) 91.2 (104) 0.01 Note. The differences in prevalence between groups were analyzed using χ2-tests. Data shown are % (n). The bold values indicate statistical significance and are bolded to improve the readability of the table. MetS, metabolic syndrome; HDL-C, high density lipoprotein cholesterol; apo, apolipoprotein. Table 3. Prevalence of MetS in Patients with Each MetS Factor according to ApoCIII Quartiles
In addition, we also found significant associations of apoCIII levels with virtually all MetS risk factors including BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), TG, total cholesterol (TC), LDL-C, non-HDL-C, apoA1: apoB, fasting glucose (FG), and hemoglobin A1C (HbA1C) (all P < 0.01) (Table 4).
Variables Crude Coefficients P-value Adjusted Coefficients P-value BMI (kg/m2) 0.135 < 0.001 0.132 < 0.001 SBP (mmHg) 0.084 0.007 0.100 0.003 DBP (mmHg) 0.089 0.005 0.086 0.011 TG (mmol/L) 0.701 < 0.001 0.700 < 0.001 TC (mmol/L) 0.411 < 0.001 0.394 < 0.001 HDL-C (mmol/L) 0.015 0.569 0.012 0.624 LDL-C (mmol/L) 0.175 < 0.001 0.153 < 0.001 Non-HDL-C (mmol/L) 0.446 < 0.001 0.429 < 0.001 apoA1 (g/L) 0.160 < 0.001 0.135 < 0.001 apoB (g/L) 0.342 < 0.001 0.315 < 0.001 Glucose (mmol/L) 0.109 < 0.001 0.119 < 0.001 HbA1C (%) 0.151 < 0.001 0.134 < 0.001 WBC (×109/L) 0.100 < 0.001 0.085 0.011 hs-CRP (mg/L) 0.116 < 0.001 0.112 < 0.001 Note. The Pearson correlation coefficients are shown. Log-transformed TG, hs-CRP, and apoCIII levels were used in the analysis. The adjusted coefficients were adjusted for age and gender. The bold values indicate statistical significance and are bolded to improve the readability of the table. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; Non-HDL-C, non-high density lipoprotein cholesterol; apo, apolipoprotein; HbA1C, hemoglobin A1C; hs-CRP, high sensitivity C-reactive protein; WBC, white blood cell. Table 4. Correlations of apoCIII with Metabolic and Inflammatory Parameters
Finally, regression analyses were performed according to apoCIII levels and each MetS component to determine the extent to which apoCIII levels affected the association of MetS risk components with MetS development (Figure 2). We considered patients with levels of apoCIII ≤ 86.8 μg/mL (the median of the study population) as the low apoCIII group, and patients with levels > 86.8 μg/mL as the high apoCIII group. Patients who had low apoCIII and no MetS components were regarded as the reference group (OR = 1). Our data revealed that there were significant interactions between apoCIII levels and each MetS component in the development of MetS, since elevated risks of developing MetS were observed with high apoCIII in patients with each metabolic component. The adjusted ORs of high apoCIII (vs. low apoCIII) in overweight/obese, hypertensive, hypertriglycerid- emic, hypo HDL cholesterolemic and hyperglycemic subjects for MetS were 27.2 (vs. 14.6), 51.6 (vs. 28.1), 2.6 (vs. 1.7), 5.4 (vs. 3.9), and 29.6 (vs. 10.0), respectively.
Figure 2. The adjusted odds ratios (ORs) for MetS incidence by difference status of MetS risk components and apoCIII levels [overweight/obesity (A), hypertension (HT) (B), hypertriglyceridemia (HTG) (C), hypo HDL cholesterolemia (D), hyperglycemia (E)], (low apoCIII ≤ 86.8 μg/mL; high apoCIII > 86.8 μg/mL).
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Consistent with the findings of previous studies [13], our data also showed that the markers of inflammation including levels of white blood cells (WBC) and high sensitivity C-reactive protein (hs-CRP) were significantly and positively correlated with the presence of MetS (Table 1), and levels of both hs-CRP and WBC were increased with the number of risk components (Figure 1). The patterns of findings in univariable and multivariable logistic regression analyses, with adjustment for age and gender, were essentially unchanged from their correlations, suggesting that WBC and hs-CRP levels were significant predictors of MetS (data not shown in Table).
Furthermore, as shown in Table 4: the levels of apoCIII were significantly and positively correlated with the inflammatory markers (WBC r = 0.100: P < 0.001, hs-CRP r = 0.116: P < 0.001, respectively). The correlations remained significant after adjustment for age and gender (WBC r = 0.085: P = 0.011, hs-CRP r = 0.112: P < 0.001, respectively).
Finally, in a model with MetS as the dependent variable, WBC or hs-CRP level as the independent variable, and apoCIII level as the mediator variable, with age, sex, and TG as covariates, the role of apoCIII level in the association of inflammation with MetS was evaluated (Table 5). Data from mediation analyses indicated that there was a 12.5% difference in MetS susceptibility that was attributed to the different hs-CRP levels (P < 0.001) and that 26.4% of this difference was mediated by increased apoCIII level (3.3% of the difference in MetS susceptibility was mediated by apoCIII level; P < 0.001 for the mediation effect). The apoCIII level had a similar mediation effect on the association between WBC and MetS incidence, and the effect size was 9.8%.
Mediator Models Parameters Effect Size for MetS P-value apoCIII hs-CRP Total effect of inflammation 0.125 < 0.001 Effect not mediated by apoCIII 0.092 0.005 Effect mediated by apoCIII 0.033 < 0.001 Proportion of inflammation effect mediated by apoCIII 26.4 apoCIII WBC Total effect of inflammation 0.088 0.002 Effect not mediated by apoCIII 0.082 0.015 Effect mediated by apoCIII 0.006 0.021 Proportion of inflammation effect mediated by apoCIII 6.8 Note. Mediation analyses with apoCIII as a mediator for the associations of inflammation with MetS development were performed. The analysis is shown after adjustment for age, gender, and TG. The bold values indicate statistical significance and are bolded to improve the readability of the table. apoCIII, apolipoprotein CIII; MetS, metabolic syndrome; hs-CRP, high sensitivity C-reactive protein; WBC, white blood cell. Table 5. The Role of apoCIII Level in the Association between Inflammation and MetS Development Evaluated by Mediation Analyses