Vitamin d deficiency and metabolic syndrome: The joint effect on cardiovascular and all-cause mortality in the United States adults

Table 1 Characteristics of participants at baseline

	Serum 25(OH)D concentrations									P value
	< 20 ng/mL			20 to 29 ng/mL			≥ 30 ng/mL
	No.	mean, %	(SE)	No.	mean, %	(SE)	No.	mean, %	(SE)
MetS, %										< 0.001
No	2640	64.7		2230	70.8		1276	79.3
Yes	1394	35.3		1089	29.2		465	20.7
Age, yr	4034	45.8	(0.6)	3319	44.7	(0.6)	1741	40.3	(0.6)	< 0.001
Waist circumference, cm	4034	94.2	(0.4)	3319	92.2	(0.3)	1741	88.3	(0.4)	< 0.001
Body mass index, kg/m2	4033	27.8	(0.2)	3318	26.5	(0.1)	1739	25.0	(0.1)	< 0.001
Systolic BP, mmHg	4034	123.4	(0.6)	3319	122.0	(0.6)	1741	119.0	(0.6)	<0.001
Diastolic BP, mmHg	4034	74.7	(0.3)	3317	74.1	(0.3)	1741	72.9	(0.4)	< 0.001
Triglycerides, mg/dL	4034	138.9	(4.1)	3319	136.4	(2.6)	1741	126.5	(3.8)	< 0.001
HDL-C, mg/dL	4034	51.0	(0.5)	3319	49.3	(0.4)	1741	51.5	(0.6)	< 0.001
Glucose, mg/dL	4034	100.7	(0.7)	3319	98.4	(0.5)	1741	94.7	(0.4)	< 0.001
Categorical variable, %
Sex, male, %	1561	38.3		178	51.9		975	55.4		< 0.001
Race/ethnicity, %										< 0.001
NHW	894	55.1		1557	79.7		1213	92.0
NHB	1788	25.8		575	6.0		139	1.9
Others	1352	19.1		1187	14.3		389	6.1
Region										< 0.001
Northeast	490	15.8		429	20.6		303	26.7
Midwest	651	18.9		709	24.5		434	28.1
South	1933	40.3		1299	33.2		685	29.1
West	960	25.0		882	21.6		319	16.1
Education level										0.001
< High school	930	13.1		818	11.8		355	8.2
High school	1971	49.2		1532	45.8		788	46.1
> High school	1113	37.7		949	42.4		592	45.6
Smoking										0.07
Never	2562	62.1		2230	63.9		1130	62.5
Former	193	5.5		191	6.0		105	4.0
Current	1279	32.4		898	30.2		506	33.5
Alcohol consumption, yes	1704	44.8		1592	55.9		910	63.7		< 0.001
Exercise, yes										0.13
More activity	559	14.1		475	16.3		287	18.4
About the same	2433	58.3		1998	56.2		1005	52.7
Less activity	1040	27.6		841	27.5		445	28.9
Health conditions
Hypertension, yes	1489	36.5		1129	29.6		565	25.5		< 0.001
Diabetes mellitus	465	9.3		312	6.7		105	3.3		< 0.001
CVD	278	6.3		252	5.3		124	3.4		0.001

Weighted mean and percentage are estimated because NHANES III applied a complex, multistage, probability sampling design. SE: Standard error; MetS: Metabolic syndrome; BP: Blood pressure; HDL-C: High-density lipoprotein cholesterol; NHW: Non-Hispanic White; NHB: Non-Hispanic Black; Others: Including all the other race/ethnicity groups; CVD: Cardiovascular disease included those with coronary heart disease, heart failure, or stroke.

Table 2 Age-sex-adjusted mortality from heart disease, cerebrovascular disease, cardiovascular disease, and all-cause mortality

	Observed number		Weighted mortalityrate per 10000 PY		P value
	No. at risk	Case	Rate	(95%CI)
Heart Disease
25(OH)D, ng/mL
≥ 30	1741	130	11.7	(8.2-16.6)	Ref.
20-29	3319	272	13.2	(10.3-16.9)	0.43
< 20	4034	292	17.4	(13.1-23.0)	0.012
CBVD
25(OH)D, ng/mL
≥ 30	1741	34	3.6	(2.0-6.6)	Ref.
20-29	3319	83	3.6	(2.5-5.1)	0.97
< 20	4034	88	4.5	(2.5-7.9)	0.53
CVD
25(OH)D, ng/mL
≥ 30	1741	164	15.3	(11.4-20.5)	Ref.
20-29	3319	355	16.6	(13.3-20.7)	0.56
< 20	4034	382	21.3	(16.6-27.3)	0.023
All-cause
25(OH)D, ng/mL
≥ 30	1741	545	75.9	(64.9-88.8)	Ref.
20-29	3319	1141	87.5	(79.4-96.3)	0.066
< 20	4034	1290	103.9	(93.2-115.8)	< 0.001
MetS status
Heart Disease
MetS, no	6146	327	12.5	(9.7-16.2)	Ref.
MetS, yes	2948	369	16.7	(12.9-21.7)	0.002
CBVD
MetS, no	6146	97	3.2	(2.2-4.7)	Ref.
MetS, yes	2948	108	5.1	(2.9-8.9)	0.059
CVD
MetS, no	6146	424	15.9	(13.0-19.5)	Ref.
MetS, yes	2948	477	22.0	(16.9-28.6)	< 0.001
All-cause
MetS, no	6146	1490	82.5	(75.3-90.5)	Ref.
MetS, yes	2948	1486	102.4	(91.0-115.3)	< 0.001

PY: Person-years; CBVD: Cerebrovascular disease; CVD: Cardiovascular disease; 25(OH)D: Serum 25 hydroxyvitamin D concentration; MetS: Metabolic syndrome.

Table 3 Hazard ratios of serum 25 hydroxyvitamin D concentration and metabolic syndrome for heart disease, cerebrovascular disease, cardiovascular disease, and all-cause mortality

	Model 1			Model 2
	HR	(95%CI)	P value	HR	(95%CI)	P value
Ref to 25(OH)D ≥ 30 ng/dL
25(OH)D for HD
20-29	1.13	(0.82-1.55)	0.45	1.13	(0.83-1.52)	0.43
< 20	1.54	(1.14-2.08)	0.005	1.43	(1.07-1.91)	0.017
25(OH)D for CBVD
20-29	0.97	(0.61-1.53)	0.88	0.98	(0.62-1.56)	0.94
< 20	1.15	(0.58-2.26)	0.69	1.14	(0.58-2.25)	0.69
25(OH)D for CVD
20-29	1.09	(0.82-1.46)	0.54	1.10	(0.82-1.46)	0.52
< 20	1.44	(1.09-1.91)	0.011	1.36	(1.04-1.78)	0.028
25(OH)D for all-cause mortality
20-29	1.16	(0.99-1.35)	0.06	1.16	(0.99-1.36)	0.07
< 20	1.38	(1.16-1.64)	0.001	1.32	(1.10-1.58)	0.004
Ref to Non-MetS
MetS for HD	1.31	(1.09-1.58)	0.005	1.22	(1.00-1.49)	0.053
MetS for CBVD	1.58	(0.94-2.66)	0.083	1.60	(0.96-2.65)	0.069
MetS for CVD	1.37	(1.12-1.66)	0.002	1.29	(1.05-1.59)	0.017
MetS for all-cause mortality	1.22	(1.08-1.37)	0.002	1.20	(1.05-1.36)	0.008
Interaction of
25(OH)D x MetS on
HD	0.91	(0.72-1.17)	0.46	0.91	(0.72-1.15)	0.41
CBVD	0.80	(0.39-1.66)	0.54	0.79	(0.38-1.62)	0.50
CVD	0.89	(0.71-1.12)	0.31	0.88	(0.70-1.11)	0.28
All-cause	0.98	(0.84-1.14)	0.78	0.96	(0.82-1.13)	0.63

Model 1 adjusted for age, sex, race/ethnicity, education, and regions; Model 2 adjusted covariate in Model 1 plus smoking status, physical activity, alcohol consumption, and baseline CVD. HR: Hazard ratio; 25(OH)D: Serum 25 Hydroxyvitamin D concentration; HD: Heart disease; CBVD: Cerebrovascular disease; CVD: Cardiovascular disease; MetS: Metabolic syndrome.

Table 4 Top 10 important predicators for classifying serum 25 Hydroxyvitamin D levels in the total and sex-specific samples

	S1: In both sex		S2: In males		S3: In females		S4: In both sex		S5: In males		S6: In females
	≥ 20 vs < 20		≥ 20 vs < 20		≥ 20 vs < 20		≥ 30 vs < 30		≥ 30 vs < 30		≥ 30 vs < 30
Rank	Predictor	MDG	Predictor	MDG	Predictor	MDG	Predictor	MDG	Predictor	MDG	Predictor	MDG
1	Race	519.5	Race	229.7	Race	267.7	Race	200.0	Race	95.2	Race	103.9
2	Folate	90.4	RBP	19.6	Folate	101.3	Age	97.5	WC	34.0	Age	79.4
3	Sex	57.3	Age	14.8	Age	77.5	Folate	65.1	BMI	29.0	GFR	50.6
4	Region	34.3	Glucose	14.2	GFR	73.7	GFR	54.8	AGE	28.9	Folate	49.6
5	RBP	34.0	GFR	13.1	RBP	50.7	BMI	48.8	Region	24.8	RBP	34.1
6	Poverty	33.3	Poverty	12.8	Poverty	50.1	WC	42.2	GFR	22.7	WC	32.0
7	Edu	30.3	Region	11.9	WC	22.9	Poverty	41.4	Insulin	18.9	SBP	26.9
8	GFR	29.6	WC	11.1	VEP	21.1	RBP	39.8	C1P	18.8	BMI	23.2
9	UAP	27.7	Folate	10.9	SBP	16.1	Glucose	22.0	RBP	18.6	VEP	22.0
10	Alcoh	21.6	Edu	9.8	A1C	14.6	DairyHEI	20.8	Poverty	17.4	Poverty	18.8
Accuracy,%	71.1		70.8		68.0		81.5		79.3		81.8
Precision, %	68.4		68.2		68.2		83.0		82.4		85.6
Recall,%	63.0		47.5		68.5		97.0		93.5		94.0
F1 score, %	65.6		56.0		68.3		89.5		87.6		89.6

S1-S3: Samples 1 to 3. S1 to S3 for the classification of serum 25(OH)D ≥ 20 vs <20 ng/mL. Of them, S1: In the total sample. S2: In males. S3: In females. S4-S6: Samples 4 to 6. S4 to S6 for the classification of serum 25(OH)D ≥ 30 vs <30 ng/mL. Of them, S4: in the total sample. S5: In males. S6: In females. MDG: Mean decrease in Gini index. A higher MDG index indicates higher variable importance; RBP: Red blood cell folate; Edu: Educational level; GFR: Glomerular filtration rate; UAP: Serum uric acid; Alcohol: Alcohol consumption; WC: Waist circumference; BMI: Body mass index; VEP: Serum concentrations of vitamin E; SBP: Systolic blood pressure; A1C: Hemoglobin A1c; DairyHEI: Dairy healthy eating index; C1P: Serum C-peptide.