Prognosis of unrecognized coeliac disease as regards mortality: A population-based cohort study

Figures & data

Table

Celikey	a test for immunoglobulin A (IgA)-class
EMA	a test for IgA endomysial antibodies
Eu-tTG	a test for IgA-class tissue transglutaminase antibodies (Eu-tTG® umana IgA, Eurospital S.p.A., Trieste, Italy)
ICD	International Classification of Diseases
IgA	Immunoglobulin
tTG	tissue transglutaminase antibodies (Celikey®, Phadia, Freiburg, Germany)

Figure 1.  Flow chart of the present study. Eu-tTG = IgA-class tissue transglutaminase antibody (Eu-tTG® umana IgA); Celikey tTG = IgA-class tissue transglutaminase antibody (Celikey® Tissue Transglutaminase IgA Antibody Assay); EMA = immunoglobulin A (IgA)-class endomysial antibody; a = Not including non-participants in the primary study (n=783) or participants with no sera available for the purposes of the current study in 2001 (n=227); b = Cases with previous coeliac disease or dermatitis herpetiformis diagnosis (n=3).

Table I.  Association of personal characteristics with endomysial (EMA) and tissue transglutaminase (Celikey tTG) antibodies: age- and sex-adjusted distributions or mean values with standard deviations (SD) are shown.

	EMA		Celikey tTG
Variable	Negative (n=6913)	Positive n(n=74)	P-value	Negative (n =6783)	Positive (n =204)	P-value
Men ^a,%	46.3	28.0	0.002	46.3	38.7	0.03
Age ^b, years (SD)	51.1 (14.1)	49.2 (11.8)	0.26	50.8 (14.0)	59.1 (14.2)	<0.001
Intermediate or higher education,%	32.4	36.1	0.47	32.3	32.4	0.98
Body mass index, kg/m^2 (SD)	25.9 (4.1)	25.0 (3.9)	0.07	25.9 (4.1)	25.6 (4.4)	0.32
Smokers,%	23.7	19.6	0.38	23.8	19.0	0.10
Physically active,%	15.3	15.1	0.96	15.3	13.7	0.52
Alcohol consumption, g/week (SD)	45.9 (107.8)	33.8 (80.8)	0.31	45.3 (106.1)	60.8 (149.7)	0.03
Hypertensive,%	22.7	20.2	0.60	22.6	26.5	0.18
Total cholesterol, mmol/L (SD)	6.95 (1.37)	6.36 (1.16)	<0.001	6.96 (1.36)	6.37 (1.36)	<0.001
HDL, mmol/L (SD)	1.70 (0.41)	1.50 (0.32)	<0.001	1.70 (0.41)	1.55 (0.38)	<0.001
Triglycerides, mmol/L (SD)	1.54 (1.08)	1.38 (0.49)	0.19	1.53 (1.08)	1.50 (0.73)	0.67
LDL, mmol/L (SD)	4.56 (1.24)	4.24 (1.04)	0.02	4.57 (1.24)	4.15 (1.18)	<0.001
Diabetes,%	5.7	3.3	0.35	5.5	11.1	<0.001
Coronary disease,%	10.9	5.8	0.14	10.9	10.0	0.66
Stroke,%	1.6	1.7	0.95	1.5	3.1	0.08
Cancer,%	2.2	1.4	0.64	2.2	0.1	0.03

^aAge-adjusted.

^bSex-adjusted.

^bHDL = serum high-density lipoprotein; LDL = serum low-density lipoprotein.

Table II.  Age-, sex-, and multivariate-adjusted relative risks of all-cause mortality between persons with positive and negative endomysial (EMA) and tissue transglutaminase (Celikey tTG) antibodies.

		Mortality, relative risks
Antibody	Deaths/persons at risk	Age- and sex-adjusted (95% CI, P-value)	Multivariate-adjusted ^a (95% CI, P-value)	Multivariate-adjusted ^b (95% CI, P-value)
EMA
Positive	23/74	0.78 (0.52–1.18, 0.22)	0.91 (0.59–1.38, 0.64)	0.85 (0.57–1.29, 0.44)
Negative	3046/6913	1.0	1.0	1.0
Celikey tTG
Positive	128/204	1.19 (0.99–1.42, 0.07)	1.18 (0.99–1.42, 0.08)	1.20 (1.00–1.43, 0.06)
Negative	2941/6783	1.0	1.0	1.0

^aAdjusted for sex, age, education, body mass index, smoking, alcohol consumption, hypertension, serum cholesterol, serum high-density lipoprotein, serum triglycerides, diabetes, coronary disease, stroke, and cancer.

^bAdjusted only for sex, age, education, alcohol consumption, smoking, and diabetes. CI = confidence intervals.

Table III.  Age- and sex-adjusted relative risks of cause-specific mortality between persons with positive and negative endomysial (EMA) and tissue transglutaminase (Celikey tTG) antibodies.

	EMA				Celikey tTG
Cause of death ^a (ICD code ^b)	Negative (n=6913)	Positive (n=74)	RR ^c (95% CI) ^d	P-value	Negative (n =6783)	Positive (n=204)	RR ^c (95% CI) ^d	P-value
Malignant neoplasm (C00–C97)	655	5	0.73 (0.30–1.77)	0.47	641	19	0.87 (0.55–1.38)	0.56
Digestive organs (C15–C26)	234	1	0.41 (0.06–2.89)	0.29	223	12	1.55 (0.86–2.78)	0.17
Lymphoma (C81–C88)	20	2	9.51 (2.20–41.22)	0.02 ^f	20	2	2.69 (0.62–11.63)	0.24
Diseases of the circulatory system (I00–I99)	1539	12	0.85 (0.48–1.50)	0.57	1482	69	1.23 (0.97–1.57)	0.10
Ischaemic heart diseases (I20–I25)	930	4	0.49 (0.19–1.30)	0.10	904	30	0.90 (0.62–1.30)	0.56
Stroke (I60–I69)	354	4	1.20 (0.45–3.23)	0.72	334	24	1.82 (1.20–2.76)	0.01^e
Diseases of the digestive system (K00–K93)	94	0	-	-	91	3	0.96 (0.30–3.05)^e	0.95
Endocrine diseases (E00–E35)	42	0	-	-	40	2	1.27 (0.31–5.30)^e	0.75
Diseases of the respiratory system (J00–J99)	260	3	1.47 (0.47–4.61)^e	0.53	246	17	1.76 (1.08–2.90)^e	0.04^f
Dementia (F00–F03, G30, R54)	152	1	0.70 (0.10–5.04)	0.71	142	11	2.31 (1.25–4.28)	0.02^f
Accidents, suicide and violence (S00–S99; T00–T98; V01–V99; W00–W99; X00–X99; Y00–Y98)	160	1	0.63 (0.09–4.50)^e	0.62	158	3	0.64 (0.20–2.01)^e	0.41

^aDue to the low number (0–1) of cases with diseases of the nervous system, infectious and parasitic conditions, musculoskeletal system and connective tissue diseases or specific malignancies as cause of death in the antibody-positive group, the results are not shown.

^bRelevant International Classification of Diseases codes (ICD-8, -9, and -10) were used. Corresponding ICD-10 codes are shown.

^cRelative risk estimated by a Cox regression model.

^dThe analysis was repeated after exclusion of cases with the mentioned illness at the beginning of follow-up, and the results remained virtually the same.

^eExclusion of cases with the defined illness at the beginning of follow-up was not possible.

^fP-value < 0.05.