Low serum vitamin D level associated with incident advanced liver disease in the general population – a prospective study

Figures & data

Figure 1. The functional form of the association between serum vitamin D level and incident advanced liver disease by Cox regression analysis with vitamin D modelled non-linearly using restricted cubic splines, and adjusted for age, sex and season and stratified by cohort (A), or age, sex, waist-hip ratio, body-mass index, type 2 diabetes, alcohol use (grams per week), smoking (current, former, never), exercise, season and stratified by cohort (B).

Table 1. Baseline characteristics of the whole study population.

	All subjects (mean ± SD)	Finrisk 1997 (mean ± SD)	Health 2000 (mean ± SD)	p Value
N	13807	7739	6068
Sex male / female (%)	6604/7203 (52)	3838/3901 (50)	2766/3302 (54)	<.001
Age (years)	50.5 ± 14.2	48.7 ± 13.3	52.8 ± 14.9	<.001
Education (%)				<.001
Low	4905 (36)	2520 (33)	2385 (40)
Average	4561 (33)	2614 (34)	1947 (32)
High	4243 (31)	2530 (33)	1713 (28)
Employment (%)				<.001
Part-or fulltime employed	7860 (57)	4430 (58)	3430 (57)
Other	1877 (14)	1247 (16)	630 (10)
Retired	3989 (29)	1999 (26)	1990 (33)
Marital status (%)				<.001
Married/partnership	9894 (72)	5674 (74)	4220 (70)
Single	1724 (13)	1050 (14)	674 (11)
Widow, separated, divorced	2150 (16)	995 (13)	1155 (19)
Exercise 20–30 mins per week (%)				.032
At least 2 times a week	7834 (58)	4363 (57)	3471 (59)
2–4 times a month	3786 (28)	2137 (28)	1649 (28)
Less often	1901 (14)	1122 (15)	779 (13)
Smoking (%)				.001
Current	3402 (25)	1812 (24)	1590 (26)
Former	3097 (23)	1773 (23)	1324 (22)
Never	7217 (53)	4089 (53)	3128 (52)
Alcohol use (grams of ethanol/week)	72 ± 137	70 ± 130	75 ± 145	.034
Binge drinking (how many times ≥5 drinks consumed per occasion during past 12 months)	9.9 ± 28.3	N/A	9.9 ± 28.3
BMI (kg/m^2)	26.8 ± 4.6	26.7 ± 4.5	26.9 ± 4.7	.001
Waist-hip ratio	0.88 ± 0.1	0.86 ± 0.1	0.91 ± 0.1	<.001
HOMA-IR	2.49 ± 5.40	N/A	2.49 ± 5.40
Number of the components of metabolic syndrome (%)				<.001
0	1697 (12)	1020 (13)	677 (11)
1	3445 (25)	2305 (30)	1140 (19)
2	3764 (27)	2231 (29)	1533 (25)
3	2706 (20)	1342 (17)	1364 (23)
4	1622 (12)	724 (9)	898 (15)
5	573 (4)	117 (2)	456 (8)
Fatty liver index	43.5 ± 29.1	41.1 ± 30.4	46.7 ± 27.0	<.001
S-25(OH)D (nmol/L)	39.5 ± 17.3	35.3 ± 16.3	44.9 ± 16.9	<.001
Total cholesterol (mmol/L)	5.7 ± 1.1	5.5 ± 1.1	5.9 ± 1.1	<.001
LDL cholesterol (mmol/L)	3.4 ± 1.0	3.5 ± 1.0	3.7 ± 1.1	<.001
HDL cholesterol (mmol/L)	1.4 ± 0.4	1.4 ± 0.4	1.3 ± 0.4	<.001
GGT (U/L)	35.5 ± 48.8	34.9 ± 50.5	36.1 ± 46.5	.159

BMI, body mass index; GGT, g-glutamyltransferase; HDL, high density lipoprotein; HOMA-IR, Homeostatic model assessment of insulin resistance; LDL, low density lipoprotein; SD, standard deviation.

Table 2. Hazard ratios (HR) with 95 % confidence intervals (CIs) for incident severe liver events (hospitalization, liver cancer or liver deaths) according to serum vitamin D based on Cox regression analyses in the combined FINRISK 1997 and Health 2000 cohorts. Cox regression analyses are stratified by cohort.

	HR	95 % CI	p Value
Adjusted (age and sex)	0.972	0.961–0.983	<.001
Men (adjusted for age)	0.969	0.956–0.983	<.001
Women (adjusted for age)	0.980	0.960–1.001	.064
Health 2000 cohort (adjusted for age and sex)	0.960	0.943–0.976	<.001
FINRISK 1997 cohort (adjusted for age and sex)	0.983	0.967–0.998	.027
Sensitivity analyses
Model 1	0.981	0.970–0.993	.001
Model 2	0.983	0.972–0.994	.003
Model 3	0.983	0.971–0.995	.004
Model 4	0.983	0.971–0.995	.007
Model 5	0.984	0.973–0.995	.006
Model 6	0.983	0.972–0.995	.004
Model 7	0.971	0.954–0.989	.002
Model 8	0.983	0.972–0.995	.005
Model 8	0.983	0.972–0.995	.005
Model 9	0.972	0.954–0.990	.002
Model 10	0.983	0.972–0.995	.005
All cases (n = 245, including also less severe cases), adjustment similar to Model 2	0.984	0.975–0.993	<.001
Liver events >3 years from the baseline (n = 121)
-adjusted for age, sex and season	0.979	0.967–0.991	<.001
-adjusted similar to Model 2	0.988	0.976–1.000	.049

Adjusted for:

Model 1 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise.

Model 2 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season.

Model 3 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season, GGT.

Model 4 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season, number of cigarettes per day.

Model 5 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season, employment, marital status, education.

Model 6 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season, number of metabolic factors (= of the 5 factors included in the definition of metabolic syndrome).

Model 7 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season, HOMA-IR (only available in Health 2000 cohort).

Model 8 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season, fatty liver index.

Model 9 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season, binge (frequency of drinking at least 5 drinks per day; only available in Health 2000 cohort).

Model 10 Age, sex, waist-hip-ratio, BMI, type 2 diabetes, alcohol use, smoking (current, former, never), exercise, season, cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides.