Magnesium and Zinc Intake Ratio Mediates the Increase of Coronary Artery Calcification through Upregulating Interleukin 6

Figures & data

Table 1. Baseline characteristics of study populations according to CAC score progression

Variables	No CAC progression (N = 3892)		CAC progression (N = 2922)	P value
Demographics
Age, year	59.8 (10.10)		65.2 (9.58)	<0.001
Male, N (%)	1542 (39.6)		1671 (57.2)	<0.001
Hypertension, N (%)	1510 (38.8)		1548 (53.0)	<0.001
Diabetes, N (%)	883 (22.8)		915 (31.4)	<0.001
Smoking, N (%)	1776 (45.8)		1598 (54.8)	<0.001
Alcohol, N (%)	2057 (67.5)		1692 (69.7)	0.071
Examinations
BMI, kg/m^2	28.3 (5.57)		28.4 (5.24)	0.233
SBP, mmHg	124.1 (21.44)		129.9 (21.10)	<0.001
DBP. mmHg	71.3 (10.35)		72.7 (10.08)	<0.001
PP, mmHg	52.8 (16.90)		57.2 (17.43)	<0.001
Biochemistry
Fasting glucose, mg/dl	95.5 (29.41)		99.86 (31.23)	<0.001
eGFR, ml/min/1.73 m^2	80.1 (16.03)		75.3 (16.35)	<0.001
HDL, mg/dl	52.1 (15.22)		49.5 (14.17)	<0.001
LDL, mg/dl	116.3 (31.36)		118.4 (31.57)	0.009
Cholesterol, mg/dl	193.7 (35.11)		194.8 (36.54)	0.179
Triglyceride, mg/dl	128.3 (88.17)		136.0 (89.45)	<0.001
Inflammatory markers
TNF	1316.7 (461.22)		1438.5 (445.29)	<0.001
IL 2	941.2 (443.96)		1036.2 (480.59)	<0.001
IL 6	1.5 (1.23)		1.6 (1.22)	<0.001
hsCRP	3.8 (6.07)		3.7 (5.63)	0.522
Dietary intake
Total protein,g	60.4 (32.83)		59.9 (32.06)	0.534
Total fat, g	55.0 (35.67)		53.8 (33.84)	0.211
Total carbohydrate, g	200.3 (105.34)		196.7 (98.62)	0.178
Phosphorus, mg	1035.4 (587.60)		1037.1 (588.80)	0.909
Magnesium, mg	258.4 (130.91)		262.1 (129.83)	0.259
Zinc, mg	8.2 (4.84)		8.2 (4.63)	0.902
Calcium, mg	719.0 (521.18)		719.4 (539.10)	0.972
Mg: Zn ratio	33.3 (8.23)		33.8 (8.17)	0.028
Iron, mg	12.2 (6.39)		12.3 (6.07)	0.846
Cupper, mg	1.1 (0.62)		1.1 (0.58)	0.954
Sodium, mg	2154.7 (1276.21)		2134.7 (1222.49)	0.534
Potassium, mg	2611.0 (1308.49)		2653.3 (1319.50)	0.208
B6, mg	1.6 (0.79)		1.6 (0.76)	0.278
B12, mcg	3.6 (3.35)		3.5 (2.83)	0.625
Folate, mcg	360.0 (186.93)		356.8 (177.94)	0.489
Folate: B12	157.3 (843.07)		138.5 (117.36)	0.252
Calcium:phosphorus	0.7 (0.16)		0.7 (0.16)	0.511
Vitamin Supplements, N (%)		2138 (60.6)	1629 (61.2)	0.616

*BMI; body mass index, SBP; systolic blood pressure, DBP; diastolic blood pressure, PP; pulse pressure, HDL; high-density lipoprotein cholesterol, LDL, low-density lipoprotein cholesterol, eGFR; estimated glomerular filtration rate, TNF-α; tumor necrosis factor alpha, IL-2; Interleukin-2, IL-6; interleukin-6, CACS; coronary artery calcium score, F-Glu; Fasting glucose, CRP; C-reactive protein, B6; Vitamin B6

Figure 1. The association between dietary intake of Mg:Zn and coronary artery calcification. (1A) higher Mg:Zn intake was associated with increased baseline CAC, (1B) follow-up CAC, and (1 C) CAC progression.

Table 2. Multivariable logistic regression demonstrating the association between Mg:Zn ratio and CACS progression

Dietary Mg:Zn models	OR	95% CI	P value
Model 1 (Curde)	1.007	1.001, 1.014	0.028
Model 2 (It was adjusted with age gender, smoking, alcohol consumption, hypertension, diabetes, BMI, SBP, DBP, PP, serum fasting glucose, triglycerides, cholesterol, HDL-C, LDL-C, eGFR, IL-6)	1.064	1.018, 1.111	0.005
Model 3 (It was adjusted with serum PO4, serum PTH, vitamin supplements, total energy intake, dietary calcium, vitamin B6, B12, and folate)	1.050	1.003, 1.099	0.038

*BMI; body mass index, SBP; systolic blood pressure, DBP; diastolic blood pressure, PP; pulse pressure, HDL-C; high density lipoprotein cholesterol, LDL-C, low density lipoprotein cholesterol, eGFR; estimated glomerular filtration rate, IL-6; interleukin 6, CACS; coronary artery calcium score, PO₄; phosphate, PTH; parathyroid hormone

Table 3. The association between Mg:Zn intake with CAC score progression within subgroups of total study population

Subgroups	OR	95% CI	P value	P value for interactions
Age ≤65 years >65 years	2.571 2.381	2.139, 3.091 1.879, 3.017	<0.001* <0.001*	0.017*
Sex Female Male	1.009 1.012	1.000, 1.019 1.001, 1.023	0.060 0.040*	0.590
Hypertension present absent	1.006 1.014	0.996, 1.017 1.004, 1.024	0.242 0.006*	0.255
Diabetic status No diabetes Impaired fasting glucose Diabetes present	1.011 1.010 1.005	1.003, 1.020 0.990, 1.030 0.982, 1.030	0.007* 0.327 0.655	0.784
Renal function eGFR≥70 ml/min/1.73 m^2 eGFR<70 ml/min/1.73 m^2	1.012 1.008	1.003, 1.021 0.995, 1.022	0.010* 0.205	0.828
Smoking status No smoker Former smoker Current smoker	1.018 0.994 1.036	1.008, 1.028 0.982, 1.006 1.011, 1.061	0.001* 0.342 0.004*	0.205
Alcohol consumption No Yes	1.005 1.013	0.989, 1.021 1.003, 1.002	0.547 0.011*	0.800

*Adjusted with age, gender, smoking, hypertension, diabetes, eGFR, HDL-C, LDL-C

Figure 2. The effect of Mg:Zn intake on CAC progression was partially mediated by IL-6 [Sobel test score 2.24;(SE 0.0016); P = 0.02] in non-stratified model adjusted with gender, hypertension, DM, smoking, HDL-C, LDL-C, and eGFR. Though, TNF-α, and IL-2 showed no mediating role.