Urinary orosomucoid is associated with diastolic dysfunction and carotid arteriopathy in the general population. Cross-sectional data from the Tromsø study

Figures & data

Table 1. Study population characteristics. The Tromsø Study 2007-08, n = 7181.

	Women, n = 4095 (57%)	Men, n = 3086 (43%)	p-value
Age, yr.	63.6 ± 9.3	63.5 ± 9.1	.892
Systolic blood pressure, mmHg	140 ± 24.6	141 ± 20.6	.166
Diastolic blood pressure, mmHg	76 ± 10.2	82 ± 10.2	<.001
Body mass index, kg/m²	26.8 ± 4.6	27.4 ± 3.7	<.001
Waist circumference, cm	91.7 ± 12.0	100.4 ± 10.3	<.001
Cholesterol, mmol/l	5.9 ± 1.1	5.5 ± 1.1	<.001
HbA1C, %	5.7 ± 0.6	5.8 ± 0.7	<.001
eGFR, ml/min/1.73m²	87.9 ± 14.1	88.2 ± 13.9	.389
Urinary orosomucoid excretion, mg/L	0.28 (0.15,0.56)	0.52 (0.25,1.26)	<.001
Urinary albumin excretion, mg/L	2.00 (1.0,4.51)	3.26 (1.0,6.91)	<.001
Urinary orosomucoid-creatinine ratio, mg/g	0.41 (0.23,0.86)	0.51 (0.24,1.27)	<.001
Urinary albumin-creatinine ratio, mg/mmol	0.37 (0.22,0.74)	0.34 (0.16,0.79)	<.001
Current smoking, n (%)	786 (19.5)	524 (17.2)	.012
Diabetes ^a, n (%)	335 (8.2)	312 (10.1)	.005
Hypertension ^b, n (%)	2409 (58.8)	1934 (62.7)	<.001
Self-reported use of blood pressure treatment, n (%)	1368 (34.0)	926 (30.7)	.004
Self-reported diabetes, n (%)	213 (5.3)	195 (6.5)	.045
Included in the echo cohort, n = 2245	1248 (55.6)	997 (44.4)	.491
Included in the carotid cohort, n = 6963	3957 (56.8)	3006 (43.2)	.252

Values are given as mean (± SD) for normally distributed data and as median (interquartile range) for skewed data. eGFR: estimated glomerular filtration rate.

^aDiabetes: HbA1C ≥ 6,5% and/or self-reported diabetes and/or the use of oral antidiabetic insulin.

^bHypertension: Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90mmHg, and/or the use of blood pressure lowering medication.

Table 2. Comparing basic characteristics from the whole cohort to the subgroup with echocardiography.

	Echocardiography no Echocardiography yes
	n = 4936	n = 2233	p-value
Age, yr	62.8 ± 8,1	65.0 ± 10.9	<.001
Women, n (%)	2847 (57.7)	1241 (55.6)	.098
Systolic blood pressure, mmHg	140 ± 22.6	143 ± 23.6	<.001
Diastolic blood pressure, mmHg	78 ± 10.6	79 ± 10.6	.280
Body mass index kg/m²	27.0 ± 4.2	27.0 ± 4.2	.597
Waist circumference, cm	95.3 ± 12.1	95.7 ± 12.0	.116
Cholesterol mmol/l	5.8 ± 1.2	5.7 ± 1.1	.021
HbA1C, %	5.7 ± 0.6	5.8 ± 0.7	.016
eGFR ml/min/1.73m²	88.7 ± 13.3	86.9 ± 15.0	<.001
Urinary orosomucoid-creatinine ratio, mg/g	0.43 (0.23, 0.98)	0.47 (0.24, 1.16)	<.001
Urinary albumin-creatinine ratio, mg/mmol	0.35 (0.19, 0.72)	0.38 (0.20, 0.84)	<.001
Current smoking, n (%)	928 (19.1)	382 (17.3)	.078
Diabetes ^a, n (%)	427 (8.7)	220 (9.8)	.115
Hypertension ^b, n (%)	2887 (58.4)	1437 (64.3)	<.001

Values are given as mean (± SD) for normally distributed data and as median (interquartile range) for skewed data.

eGFR: estimated glomerular filtration rate.

^aDiabetes: HbA1C > 6,5% and/or self-reported diabetes and/or the use of oral antidiabetic insulin.

^bHypertension: Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90mmHg, and/or the use of blood pressure lowering medication.

Table 3. Spearman’s Correlation between urinary biomarkers and covariates.

	UOCR	UACR	UOE	UAE
Sex	0.08	−0.06	0.28	0.16
Age, yr	0.28	0.24	0.18	0.13
Hypertension	0.23	0.18	0.20	0.15
Diabetes	0.17	0.15	0.14	0.12
Body mass index, kg/m²	0.11	0.05	0.13	0.08
eGFR ml/min/1.73m²	−0.22	−0.11	−0.19	−0.08
Current smoking	0.04^a	0.05	0.04	0.06
Cholesterol, mmol/l	−0.05	−0.05	−0.07	−0.07
Diastolic dysfunction	0.12	0.08	0.09	0.05^b
Presence plaque	0.16	0.12	0.14	0.12
Total plaque area mm²	0.18	0.14	0.18	0.16
IMT-mean	0.23	0.17	0.22	0.16

p- value <0.001 unless otherwise stated. ^ap = .002, ^bp = .015.

Hypertension: Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90mmHg, and/or the use of blood pressure.

Lowering medication.

eGFR: estimated glomerular filtration rate.

Diabetes: HbA1C > 6,5% and/or self-reported diabetes and/or the use of oral antidiabetic insulin.

IMT: intima media thickness. UOCR: Urinary orosomucoid to creatinine ratio, mg/g. UACR: Urinary albumin to creatinine ratio, mg/mmol.

UOE: urinary orosomucoid excretion. UAE: urinary albumin excretion.

Figure 1. Urinary biomarkers in persons with and without diastolic dysfunction (error bars with 95% CI).

Table 4. Odds ratio for having subclinical cardiovascular disease.

		OR for diastolic dysfunction	OR for the presence of plaque	OR for IMT in upper quartile
Model (A).
UOCR ≥upper quartile	women:	1.78, 95% CI [0.83, 3.84], p = .141	1.38, 95% CI [1.17, 1.63], p < .001	1.48, 95% CI [1.22, 1.80], p <.001
	men:	3.78, 95% CI [1.64, 8.69], p = .002	1.35, 95% CI [1.14, 1.60], p = .001	1.31, 95% CI [1.09, 1.56], p = .003
UACR ≥upper quartile	women:	1.62, 95% CI [0.77, 3.40], p = .200	1.40, 95% CI [1.20, 1.63], p < .001	1.45, 95% CI [1.20, 1.74], p < .001
	men:	1.72, 95% CI [0.77, 3.87], p = .188	1.40, 95% CI [1.18, 1.67], p < .001	1.37, 95% CI [1.14, 1.65], p = .001
Model (B).
UOCR ≥upper quartile	women:	1.68, 95% CI [0.76, 3.73], p = .200	1.28, 95% CI [1.07, 1.51], p = .005	1.43, 95% CI [1.18, 1.74], p < .001
	men:	3.73, 95% CI [1.59, 8.78], p = .003	1.29, 95% CI [1.09, 1.54], p = .005	1.33, 95% CI [1.11, 1.60], p = .002
UACR ≥upper quartile	women:	1.65, 95% CI [0.76, 3.60], p = .205	1.30, 95% CI [1.10, 1.07], p = .002	1.38, 95% CI [1.14, 1.67], p = .001
	men:	1.46, 95% CI [0.62, 3.45], p = .384	1.37, 95% CI [1.14, 1.65], p = .001	1.35, 95% CI [1.11, 1.64], p = .003
Model ©.
UOCR ≥upper quartile	women:	1.37, 95% CI [0.59, 3.18], p = .466	1.23, 95% CI [1.03, 1.47], p = .020	1.36, 95% CI [1.11, 1.67], p = .003
	men:	3.75, 95% CI [1.55, 9.07], p = .003	1.20, 95% CI [1.00, 1.44], p = .045	1.20, 95% CI [0.99, 1.45], p = .061
UACR ≥upper quartile	women:	1.73, 95% CI [0.77, 3.88], p = .182	1.27, 95% CI [1.07, 1.49], p = .005	1.30, 95% CI [1.06, 1.59], p = .010
	men:	1.31, 95% CI [0.53, 3.20], p = .559	1.26, 95% CI [1.04, 1.53], p = .019	1.18, 95% CI [0.96, 1.45], p = .113
Model (D).
UOCR ≥upper quartile	women:	1.39, 95% CI [0.59, 3.28], p = .453	1.20, 95% CI [1.01, 1.44], p = .038	1.34, 95% CI [1.09, 1.65], p = .005
	men:	3.18, 95% CI [1.27, 7.95], p = .013	1.19, 95% CI [0.99, 1.42], p = .067	1.19, 95% CI [0.98, 1.45], p = .077
UACR ≥upper quartile	women:	1.74, 95% CI [0.78, 3.91], p = .178	1.24, 95% CI [1.05, 1.46], p = .010	1.31, 95% CI [1.07, 1.60], p = .008
	men:	1.21, 95% CI [0.48, 3.06], p = .693	1.28, 95% CI [1.05, 1.56], p = .013	1.18, 95% CI [0.96, 1.45], p = .116

Model (A) Adjusted for age. Model (B) Adjusted for (A) plus hypertension and UACR as a continuous variable in the analysis for UOCR ≥ upper quartile, and for UOCR as a continuous variable in the analysis of UACR ≥ upper quartile. Model (C) Adjusted for (B) plus diabetes, body mass index, smoking and, cholesterol. Model (D) Adjusted for (C) plus eGFR. UOCR: urinary orosomucoid to creatinine ratio, UACR: urinary albumin to creatinine ratio. IMT: Intima media thickness. UOCR/UACR quartiles: we used sex specific values. eGFR: estimated glomerular filtration rate.

Table 5. Area under the ROC curve (AUC).

		Diastolic dysfunction	Presence of plaque	IMT in upper quartile
AUC Model 1	women	0.838, 95% CI [0.769, 0.907], p≤.001	0.671, 95% CI [0.654, 0.688], p≤.001	0.735, 95% CI [0.716, 0.754], p≤.001
	men	0.764, 95% CI [0.683, 0.844], p≤.001	0.657, 95% CI [0.638, 0.638], p≤.001	0.685, 95% CI [0.665, 0.705], p≤.001
AUC Model 2	women	0.828, 95% CI [0.750, 0.905], p≤.001	0.670, 95% CI [0.652, 0.687], p≤.001	0.730, 95% CI [0.711, 0.749], p≤.001
	men	0.731, 95% CI [0.631, 0.831], p≤.001	0.654, 95% CI [0.635, 0.674], p≤.001	0.682, 95% CI [0.662, 0.703], p≤.001
AUC Difference	women	0.010, 95% CI [−0.016, 0.036], p = .456	0.002, 95% CI [−0.001, 0.005], p = .249	0.005, 95% CI [0.000, 0.009], p = .062
	men	0.033, 95% CI [−0.003, 0.068], p = .071	0.003, 95% CI [−0.001, 0.007], p = .114	0.002, 95% CI [−0.002, 0.006], p = .235

Model 1: age, hypertension, UACR as a continuous variable, UOCR quartiles, diabetes, BMI, smoke, cholesterol, eGFR.

Model 2: model 1 without UOCR quartiles.

AUC difference: model 1 versus Model 2.

UOCR: urinary orosomucoid to creatinine ratio, UACR: urinary albumin to creatinine ratio. IMT: Intima media thickness. UOCR/UACR quartiles: we used sex specific values. eGFR: estimated glomerular filtration rate.