Baseline characteristic of study population
Among 4084 participants, 2038 (49.9%) were male and 2046 (50.1%) were female, with the average age of 45.26 ± 20.31. MetS was present in 1040 study participants, while 3044 subjects didn’t meet the diagnostic criteria for MetS. Baseline characteristics were compared between MetS and non-MetS group. Subjects with MetS were older, and they had higher anthropometric parameters including: SBP, DBP, HR, BMI, WC and hip circumference. Additionally, they had higher smoking and drinking rate, higher prevalence in hypertension, diabetes, hyperlipidemia, CHD, heart failure, stroke and cancer. ALT, AST, ALP and Scr were all significantly higher in individuals with MetS. Participants with MetS were more prevalent in elevated blood metabolic and inflammatory indicators, such as TG, TC, LDL, FPG, insulin and CRP. However, lower HDL were observed in participants with MetS compared with those without MetS. Of note, MetS patients presented significantly higher blood lead [0.89 (0.55–1.45) vs. 0.77 (0.46–1.13) ug/dL, p < 0.001], cadmium [0.30 (0.18–0.54) vs. 0.24 (0.15–0.46) ug/L, p < 0.001], mercury [0.63 (0.32–1.27) vs. 0.56 (0.20–1.24) ug/L, p = 0.019] and selemium levels (187.68 ± 27.42 vs. 183.37 ± 25.72 ug/L, p < 0.001), whereas no significance was found in blood manganese concentration between MetS and non-MetS group (9.89 ± 3.61 vs. 9.88 ± 3.58 ug/L, p = 0.548). Furthermore, the distribution of blood heavy metals in population with and without MetS were presented in Fig. 2. In addition, higher urinary lead, cadmium, arsenic and tin levels were also observed in population with MetS. The details of other characteristics were showed in Table 1.
Table 1
Baseline characteristics of participants with MetS and without MetS.
Variables | MetS (n = 1040) | Non-MetS (n = 3044) | P value |
Age | 55.33 ± 16.05 | 41.82 ± 20.47 | < 0.001 |
Male | 502 (48.27%) | 1536 (50.46%) | 0.223 |
SBP | 132.32 ± 19.79 | 118.38 ± 17.47 | < 0.001 |
DBP | 79.37 ± 11.95 | 71.47 ± 11.14 | < 0.001 |
HR | 70.52 ± 11.85 | 67.86 ± 11.53 | < 0.001 |
BMI | 34.02 ± 7.26 | 27.42 ± 6.70 | < 0.001 |
WC | 112.41 ± 15.06 | 93.41 ± 16.54 | < 0.001 |
Hip circumference | 114.58 ± 15.15 | 103.06 ± 13.56 | < 0.001 |
Elevated WC | 953 (91.63%) | 1239 (40.70%) | < 0.001 |
Elevated TG | 508 (48.85%) | 177 (5.81%) | < 0.001 |
Low HDL | 691 (66.44%) | 475 (15.60%) | < 0.001 |
Elevated BP | 675 (64.90%) | 684 (22.47%) | < 0.001 |
Elevated FPG | 751 (72.21%) | 448 (14.72%) | < 0.001 |
Race | | | 0.016 |
Mexican American | 154 (14.81%) | 380 (12.48%) | |
Other Hispanic | 108 (10.38%) | 293 (9.63%) | |
Non-Hispanic White | 379 (36.44%) | 1022 (33.57%) | |
Non-Hispanic Black | 240 (23.08%) | 794 (26.08%) | |
Other Race: Including Multi-Racial | 159 (15.29%) | 555 (18.23%) | |
Physical activity | | | 0.060 |
Mild work | 367 (35.29%) | 1176 (38.63%) | |
Moderate work | 438 (42.12%) | 1160 (38.11%) | |
Vigorous work | 235 (22.60%) | 708 (23.26%) | |
Smoking | 489 (47.02%) | 1014 (33.31%) | < 0.001 |
Drinking | 152 (14.62%) | 327 (10.74%) | < 0.001 |
Hypertension | 585 (56.25%) | 763 (25.07%) | < 0.001 |
Diabetes | 350 (33.65%) | 204 (6.70%) | < 0.001 |
Hyperlipidemia | 504 (48.46%) | 775 (25.46%) | < 0.001 |
Coronary heart disease | 69 (6.63%) | 79 (2.60%) | < 0.001 |
Heart failure | 60 (5.77%) | 61 (2.00%) | < 0.001 |
Stroke | 68 (6.54%) | 97 (3.19%) | < 0.001 |
Cancer | 146 (14.04%) | 213 (7.00%) | < 0.001 |
ALT | 16 (12–23) | 21 (14–31) | < 0.001 |
AST | 19 (16–23) | 19 (16–25) | < 0.001 |
ALP | 75 (61–93) | 81 (66–98) | < 0.001 |
Scr | 72.49 (60.11–84.86) | 73.37 (61.22–89.28) | < 0.001 |
TG | 1.64 (1.09–2.23) | 0.81 (0.58–1.16) | < 0.001 |
TC | 4.77 ± 1.18 | 4.60 ± 1.03 | < 0.001 |
HDL | 1.13 ± 0.28 | 1.47 ± 0.40 | < 0.001 |
LDL | 2.80 ± 1.02 | 2.70 ± 0.88 | 0.023 |
FPG | 7.59 ± 3.08 | 5.68 ± 1.14 | < 0.001 |
Insulin | 97.62 (63.97-151.91) | 51.78 (33.93–80.61) | < 0.001 |
CRP | 3.31 (1.63–6.28) | 1.31 (0.58–3.26) | < 0.001 |
Blood heavy metals | | | |
Lead | 0.89 (0.55–1.45) | 0.77 (0.46–1.13) | < 0.001 |
Cadmium | 0.30 (0.18–0.54) | 0.24 (0.15–0.46) | < 0.001 |
Mercury | 0.63 (0.32–1.27) | 0.56 (0.20–1.24) | 0.019 |
Selemium | 187.68 ± 27.42 | 183.37 ± 25.72 | < 0.001 |
Manganese | 9.89 ± 3.61 | 9.88 ± 3.58 | 0.548 |
Urinary heavy metals | | | |
Lead | 0.34 (0.21–0.58) | 0.30 (0.16–0.53) | 0.005 |
Cadmium | 0.29 (0.17–0.52) | 0.20 (0.09–0.42) | < 0.001 |
Arsenic | 7.21 (3.81–13.25) | 6.23 (3.32–13.32) | 0.007 |
Chromium | 0.13 (0.13–0.29) | 0.13 (0.13–0.26) | 0.144 |
Barium | 0.99 (0.49–0.98) | 1.01 (0.48–0.96) | 0.860 |
Cobalt | 0.32 (0.17–0.54) | 0.33 (0.17–0.60) | 0.356 |
Cesium | 4.86 (3.09–7.14) | 4.60 (2.81–6.67) | 0.075 |
Molybdenun | 41.27 (21.94–62.93) | 39.41 (22.12–65.21) | 0.822 |
Manganese | 0.09 (0.09–0.15) | 0.09 (0.09–0.14) | 0.098 |
Antimony | 0.05 (0.03–0.07) | 0.05 (0.03–0.08) | 0.521 |
Tin | 0.54 (0.30–1.18) | 0.49 (0.22-1.00) | 0.007 |
Thallium | 0.18 (0.11–0.26) | 0.19 (0.11–0.27) | 0.624 |
Tungsten | 0.07 (0.03–0.11) | 0.06 (0.03–0.12) | 0.830 |
Abbreviations: SBP: systolic blood pressure; DBP: diastolic blood pressure; HR; heart rate; BMI: body mass index; WC: waist circumference; ALT: alanine transaminase; AST: aspartate transaminase; ALP: alkaline phosphatase; Scr: serum creatinine; TG: triglyceride; HDL: high-density lipoprotein; FPG: fasting plasma glucose; TC: total cholesterol; LDL: low-density lipoprotein; CRP: C reactive protein. |
Blood cadmium concentration in MetS and its components group
As mentioned before, higher blood cadmium levels were found in individuals with MetS. Then, we compared blood cadmium concentrations in subjects with different WC, TG, HDL, BP and FPG levels. As shown in Fig. 3, the concentrations of blood cadmium were significantly higher in participants with elevated WC [0.28 (0.17–0.49) vs. 023 (0.14–0.47) ug/L, p < 0.001], TG [0.28 (0.16–0.52) vs. 0.26 (0.15–0.47) ug/L, p = 0.029], BP [0.33 (0.19–0.60) vs. 0.23 (0.14–0.42) ug/L, p < 0.001] and FPG [0.29 (0.18–0.51) vs. 0.24 (0.15–0.47) ug/L, p < 0.001] compared with those with normal metabolic parameters. However, participants in low HDL group and normal HDL group had comparable blood cadmium levels, and no statistical significance was found [0.25 (0.15–0.47) vs. 0.26 (0.16–0.49) ug/L, p = 0.332].
Univariate analysis for MetS
The relationship between different variables and MetS were evaluated using univariate analysis. As shown in Table 2, age, BMI, smoking, drinking, ALT, AST, Scr, CRP were all risk factors for the MetS, whereas participants of Non-Hispanic Black and other race had lower risk developing MetS compared with those Mexican American. In terms of blood metals, higher blood lead (OR = 1.08, 95% CI: 1.02–1.14, p = 0.0053), cadmium (OR = 1.29, 95% CI: 1.14–1.47, p < 0.0001) and selemium levels (OR = 1.01, 95% CI: 1.00-1.01, p < 0.0001) were all associated with increased risk for MetS. Furthermore, population with increased urinary cadmium and arsenic levels were more likely to have MetS.
Table 2
Univariate analysis for MetS.
Variables | OR (95% CI) | P value |
Age | 1.04 (1.03, 1.04) | < 0.0001 |
Gender | | |
Male | Reference | |
Female | 1.09 (0.95, 1.26) | 0.2226 |
BMI | 1.13 (1.12, 1.15) | < 0.0001 |
Race | | |
Mexican American | Reference | |
Other Hispanic | 0.91 (0.68, 1.21) | 0.5207 |
Non-Hispanic White | 0.92 (0.73, 1.14) | 0.4317 |
Non-Hispanic Black | 0.75 (0.59, 0.94) | 0.0151 |
Other Race: Including Multi-Racial | 0.71 (0.55, 0.91) | 0.0082 |
Mild work | Reference |
Moderate work | 1.18 (1.02, 1.36) | 0.0223 |
Vigorous work | 0.96 (0.81, 1.14) | 0.6615 |
Smoking | 1.78 (1.54, 2.05) | < 0.0001 |
Drinking | 1.42 (1.16, 1.75) | 0.0008 |
Cancer | 2.17 (1.74, 2.71) | < 0.0001 |
ALT | 1.02 (1.02, 1.03) | < 0.0001 |
AST | 1.01 (1.00, 1.01) | 0.0008 |
ALP | 1.00 (1.00, 1.00) | 0.0907 |
Scr | 1.00 (1.00, 1.01) | 0.0009 |
CRP | 1.04 (1.03, 1.05) | < 0.0001 |
Blood heavy metals | | |
Lead | 1.08 (1.02, 1.14) | 0.0053 |
Cadmium | 1.29 (1.14, 1.47) | < 0.0001 |
Mercury | 1.02 (0.99, 1.04) | 0.2176 |
Selemium | 1.01 (1.00, 1.01) | < 0.0001 |
Manganese | 1.00 (0.98, 1.02) | 0.9263 |
Urinary heavy metals | | |
Lead | 1.23 (0.98, 1.56) | 0.0797 |
Cadmium | 1.72 (1.30, 2.27) | 0.0001 |
Arsenic | 1.00 (1.00, 1.01) | 0.0327 |
Chromium | 1.12 (0.91, 1.38) | 0.2875 |
Barium | 1.01 (0.96, 1.06) | 0.6076 |
Cobalt | 0.95 (0.78, 1.15) | 0.5880 |
Cesium | 1.03 (0.99, 1.07) | 0.1045 |
Molybdenum | 1.00 (1.00, 1.00) | 0.9860 |
Manganese | 1.04 (0.85, 1.27) | 0.7060 |
Antimony | 0.72 (0.30, 1.73) | 0.4594 |
Tin | 1.02 (0.98, 1.06) | 0.3000 |
Thallium | 0.91 (0.36, 2.28) | 0.8326 |
Tungsten | 0.63 (0.25, 1.60) | 0.3292 |
Abbreviations: BMI: body mass index; ALT: alanine transaminase; AST: aspartate transaminase; ALP: alkaline phosphatase; Scr: serum creatinine; CRP: C reactive protein; |
Multivariate logistic regression analysis of MetS
Multivariate logistic regression analysis was further performed to identify the independent risk factors for MetS and presented in Fig. 4. After adjusting confounding factors, blood cadmium remained independently associated with the presence of MetS (OR = 1.253, 95% CI: 1.059–1.478, p = 0.00829). In addition, age (OR = 1.044, 95% CI: 1.038–1.050, p < 0.00001), BMI (OR = 1.139, 95% CI: 1.124–1.155, p < 0.00001) and ALT (OR = 1.036, 95% CI: 1.026–1.046, p < 0.00001) were independent risk factors of MetS, while Non-Hispanic White (OR = 0.685, 95% CI: 0.523–0.896, p = 0.00579), Non-Hispanic Black (OR = 0.559, 95% CI: 0.417–0.749, p = 0.00010), and AST (OR = 0.970, 95% CI: 0.958–0.983, p < 0.00001) were independently negatively associated with the presence of MetS.
The association of blood cadmium and risk for MetS and its components
Both crude and adjusted models were constructed to assess the association between blood cadmium and the risk for MetS. In crude model, no covariates were adjusted, and blood cadmium was treated as continuous and categorical variables, respectively. As shown in Table 3, blood cadmium level was significantly positively related to the prevalence of MetS. Specifically, an increasement of one unit in blood cadmium was associated with 1.29 times higher risk for MetS (95% CI: 1.14–1.47, p < 0.0001). The relationship between blood cadmium and risk for MetS components were also evaluated. Higher blood cadmium was found correlated to higher risk for elevated TG, low HDL and elevated BP, while no statistical significances were found between blood cadmium and elevated WC or elevated FPG. Then, participants were equally divided into 4 groups according to the blood cadmium concentration: Q1 (blood cadmium ≤ 0.155), Q2 (0.155 < blood cadmium ≤ 0.260), Q3 (0.260 < blood cadmium ≤ 0.481), and Q4 (blood cadmium > 0.481). When treating blood cadmium as a categorical variable, highest blood cadmium concentration (Q4) had remarkably increased risk for MetS compared with those with Q1 of blood cadmium levels (OR = 1.63, 95% CI: 1.33-2.00, p < 0.0001). In the model adjusted for age, sex, BMI, race, physical activity, smoking, drinking, cancer, ALT, AST, Scr, CRP, blood lead, mercury and selemium, per 1ug/L blood cadmium increasement was associated with 1.25 times higher risk for MetS (95% CI: 1.06–1.48, p = 0.0083). When recognized as a continuous variable, the association between blood cadmium and MetS components in the adjusted model remained significant. However, compared with Q1, blood cadmium at Q4 was only associated with increased elevated risk for BP but not MetS and other MetS components.
Table 3
Association of blood cadmium and risk of MetS and its components in crude and adjusted models.
Exposure | MetS | | Elevated WC | | Elevated TG | | Low HDL | | Elevated BP | | Elevated FPG | |
OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value |
Blood cadmium | 1.29(1.14, 1.47) | < 0.0001 | 1.10(0.98, 1.24) | 0.1168 | 1.20(1.04, 1.39) | 0.0105 | 1.13(1.00, 1.29) | 0.0484 | 1.53(1.35, 1.73) | < 0.0001 | 1.12(0.99, 1.27) | 0.0710 |
Blood cadmium quartile | | | | | | | | | | | | |
Q1 | Reference | | Reference | | Reference | | Reference | | Reference | | Reference | |
Q2 | 1.28(1.03, 1.58) | 0.0240 | 1.42(1.20, 1.70) | < 0.0001 | 1.15(0.91, 1.47) | 0.2381 | 0.90(0.74, 1.09) | 0.2749 | 1.64(1.34, 2.01) | < 0.0001 | 1.39(1.14, 1.70) | 0.0013 |
Q3 | 1.75(1.43, 2.14) | < 0.0001 | 1.84(1.54, 2.19) | < 0.0001 | 1.20(0.95, 1.52) | 0.1232 | 0.88(0.73, 1.07) | 0.2051 | 2.44(2.01, 2.97) | < 0.0001 | 1.87(1.54, 2.27) | < 0.0001 |
Q4 | 1.63(1.33, 2.00) | < 0.0001 | 1.43(1.20, 1.71) | < 0.0001 | 1.24(0.98, 1.57) | 0.0686 | 0.89(0.74, 1.08) | 0.2450 | 2.87(2.36, 3.49) | < 0.0001 | 1.58(1.30, 1.93) | < 0.0001 |
P for trend | < 0.0001 | | < 0.0001 | | 0.068 | | 0.244 | | < 0.0001 | | < 0.0001 | |
Adjusted model | | | | | | | | | | | | |
Blood cadmium | 1.25(1.06, 1.48) | 0.0083 | 1.30(0.97, 1.74) | 0.0809 | 1.21(1.02, 1.44) | 0.0317 | 1.29(1.10, 1.51) | 0.0014 | 1.25(1.07, 1.45) | 0.0042 | 0.98(0.83, 1.15) | 0.8057 |
Blood cadmium quartile | | | | | | | | | | | | |
Q1 | Reference | | Reference | | Reference | | Reference | | Reference | | Reference | |
Q2 | 0.90(0.69, 1.16) | 0.4119 | 0.87(0.59, 1.28) | 0.4730 | 0.97(0.74, 1.26) | 0.7931 | 0.88(0.71, 1.09) | 0.2478 | 1.12(0.89, 1.42) | 0.3214 | 0.91(0.71, 1.16) | 0.4359 |
Q3 | 0.91(0.70, 1.18) | 0.4834 | 0.90(0.60, 1.36) | 0.6297 | 0.89(0.67, 1.17) | 0.4021 | 0.92(0.74, 1.16) | 0.4950 | 1.13(0.89, 1.44) | 0.2998 | 0.82(0.64, 1.06) | 0.1287 |
Q4 | 1.05(0.79, 1.40) | 0.7481 | 1.12(0.72, 1.75) | 0.6031 | 1.00(0.74, 1.36) | 0.9901 | 1.04(0.81, 1.34) | 0.7553 | 1.51(1.17, 1.95) | 0.0018 | 0.82(0.63, 1.08) | 0.1671 |
P for trend | 0.673 | | 0.560 | | 0.888 | | 0.726 | | 0.0003 | | 0.136 | |
Adjusted model: adjusted for age, sex, BMI, race, physical activity, smoking, drinking, cancer, ALT, AST, Scr, CRP, blood lead, mercury and selemium. Abbreviations: MetS: metabolic syndrome; WC waist circumference; TG: triglyceride; HDL: high-density lipoprotein; BP: blood pressure; FPG: fasting plasma glucose; OR: odds ratio. |
Association of blood cadmium and risk for MetS in different subgroups
Stratified multiple logistic regression analysis were performed in different age, gender and race groups to explore potential heterogeneities. Table 4 showed the associations between blood cadmium levels and the risk for MetS in different age, gender and race groups. The associations between MetS and blood levels of cadmium remained significant in subjects less than 60 years old (OR = 1.33, 95% CI: 1.08–1.64; p = 0.0078) and females (OR = 1.35, 95% CI: 1.08–1.70, p = 0.0089). While no significant associations were present between blood cadmium and the risk for MetS in population elder than 60, males and any race.
Table 4
Association between blood cadmium and MetS, stratified by age, gender and race.
Blood cadmium | OR (95% CI) | P value | P for interaction |
Age | | | 0.0002 |
≤ 60 | 1.33 (1.08, 1.64) | 0.0078 | |
> 60 | 1.15 (0.87, 1.51) | 0.3201 | |
Gender | | | |
Male | 1.24 (0.96, 1,61) | 0.1021 | 0.1313 |
Female | 1.35 (1.08, 1.70) | 0.0089 | |
Race | | | 0.7204 |
Mexican American | 1.10 (0.50, 2.42) | 0.8055 | |
Other Hispanic | 1.63 (0.71, 3.78) | 0.2506 | |
Non-Hispanic White | 1.25 (0.96, 1.62) | 0.0945 | |
Non-Hispanic Black | 1.21 (0.89, 1.63) | 0.2200 | |
Other Race: Including Multi-Racial | 1.51 (0.94, 2.43) | 0.0867 | |
Abbreviations: OR: odds ratio. |