Normal Gastrointestinal Mucosa at Biopsy and Overall Mortality: Nationwide Population-Based Cohort Study

Figures & data

Table 1 Characteristics of Individuals with a GI Biopsy Result of Normal Mucosa and Their Matched References, a Nationwide Matched Cohort Study in Sweden, 1965–2016

	No. (%)
Characteristics	Normal Mucosa (n = 466,987)	Reference (n = 2,321,217)
Age at cohort entry, years ^a
Mean ± SD	44.38 ± 20.55	44.28 ± 20.53
Median (IQR)	43.90 (27.60–60.46)	43.76 (27.52–60.32)
<18 y	40,551 (8.68)	203,184 (8.75)
18-<40 y	164,204 (35.16)	818,927 (35.28)
40-<60 y	142,615 (30.54)	708,581 (30.53)
≥60 y	119,617 (25.61)	590,525 (25.44)
Gender
Male	178,262 (38.17)	886,073 (38.17)
Female	288,725 (61.83)	1,435,144 (61.83)
Country of birth
Nordic country	421,520 (90.26)	2,045,602 (88.13)
Other country	45,467 (9.74)	275,615 (11.87)
Biopsy location ^b
Upper GI	283086 (60.62)	1,407,460 (60.63)
Lower GI	183901 (39.38)	913,757 (39.37)
Start year of follow-up
1969–1989	41,709 (8.93)	207,527 (8.94)
1990–1999	119,339 (25.56)	593,460 (25.57)
2000–2009	179,118 (38.36)	889,927 (38.34)
2010–2016	126,821 (27.16)	630,303 (27.15)
Educational attainment
0–9 y	103,436 (22.15)	519,435 (22.38)
10–12 y	173,307 (37.11)	837,426 (36.08)
≥13 y	114,523 (24.52)	571,222 (24.61)
Missing	75,721 (16.21)	393,134 (16.94)
Number of health care visits
0	288,449 (61.77)	1,720,903 (74.14)
1	72,156 (15.45)	286,539 (12.34)
2–3	56,405 (12.08)	188,407 (8.12)
≥4	49,977 (10.70)	125,368 (5.40)
Charlson comorbidity index
0	354,833 (75.98)	1,979,161 (85.26)
1	80,707 (17.28)	260,117 (11.21)
≥2	31,447 (6.73)	81,939 (3.53)
History before start of follow-up
GI disease	220,054 (47.12)	353,573 (15.23)
Endoscopy	148,804 (31.86)	58,577 (2.52)
GI cancer	2728 (0.58)	3057 (0.13)
Colectomy or protocolectomy	359 (0.08)	412 (0.02)
Follow-up years, Median (IQR)	10.98 (5.63–18.03)	11.24 (5.88–18.27)
<5 y	102,445 (21.94)	478,427 (20.61)
5-<10 y	111,079 (23.79)	556,944 (23.99)
10-<25 y	212,428 (45.49)	1,073,465 (46.25)
≥25 y	41,035 (8.79)	212,381 (9.15)
No. of event
All-cause mortality	85,859 (18.39)	377,653 (16.27)
CVD mortality	28,605 (6.13)	145,773 (6.28)
Cancer mortality	24,360 (5.22)	89,137 (3.84)
GI disease mortality	3819 (0.82)	11,122 (0.48)
Other mortality	29,075 (6.23)	131,621 (5.67)

Notes: ^aCohort entry: date of first biopsy record for individuals with a GI biopsy result of normal mucosa, and date of selection for the matched references. ^b References were assigned a value of biopsy location based on the index person.

Abbreviations: IQR, interquartile range; SD, standard deviation; GI, gastrointestinal.

Table 2 Mortality in Individuals with a GI Biopsy Result of Normal Mucosa and Their Matched References

	No. of events		Incidence Rate (95% CIs), Per 10,000 PYs		Incidence Rate Difference (95% CIs), Per 10,000 PYs	HR (95% CIs)
Events	Normal Mucosa	References	Normal Mucosa	References		Model 1	Model 2
All-cause mortality	85,859	377,653	147.56 (146.59–148.55)	127.90 (127.49–128.30)	19.66 (18.60–20.73)	1.38 (1.37–1.39)	1.21 (1.20–1.22)
CVD mortality	28,605	145,773	49.16 (48.60–49.73)	49.37 (49.12–49.62)	−0.21 (−0.83–0.42)	1.16 (1.15–1.18)	1.02 (1.01–1.03)
Cancer mortality	24,360	89,137	41.87 (41.34–42.39)	30.19 (29.99–30.39)	11.68 (11.12–12.24)	1.73 (1.71–1.76)	1.58 (1.56–1.61)
GI disease mortality	3819	11,122	6.56 (6.36–6.78)	3.77 (3.70–3.84)	2.80 (2.58–3.02)	2.16 (2.07–2.24)	1.65 (1.58–1.71)
Other mortality	29,075	131,621	49.97 (49.40–50.55)	44.58 (44.34–44.82)	5.39 (4.77–6.02)	1.27 (1.26–1.29)	1.10 (1.08–1.11)

Notes: Model 1: conditioned on matching set (birth year, gender, county of residence, and calendar period). Model 2: conditioned on matching set and further adjusted for country of birth, educational attainment, number of health care visits, Charlson comorbidity index, and history of GI diseases.

Abbreviations: CIs, confidence intervals; CVD, cardiovascular disease; GI, gastrointestinal; HR, hazard ratio; PYs, Person-years.

Figure 1 The HR and 95% CI of all-cause and cause-specific mortality as a function of time since biopsy, comparing individuals with a GI biopsy result of normal mucosa with their matched references. Estimated by the flexible parametric model that conditioned on matching set (birth year, gender, county of residence, and calendar period) and further adjusted for country of birth, educational attainment, number of health care visits, Charlson comorbidity index, and history of GI diseases.

Figure 2 Subgroup analyses of the associations between normal mucosa and risk of mortality. Individuals biopsied in childhood (age at cohort entry<18 y) demonstrated a much higher risk for all-cause mortality (HR = 2.38; 95% CI: 2.11–2.69), cancer mortality (HR = 2.92; 95% CI: 2.11–4.05) and other cause of mortality (HR = 2.23; 95% CI: 1.95–2.56). Estimated by the flexible parametric model that conditioned on matching set (birth year, gender, county of residence, and calendar period) and further adjusted for country of birth, educational attainment, number of health care visits, Charlson comorbidity index, and history of GI diseases.

Table 3 Mortality in Individuals with a GI Biopsy Result of Normal Mucosa and Their Siblings

	No. of Events		Incidence Rate (95% CIs), Per 10,000 PYs		Incidence Rate Difference (95% CIs), Per 10,000 PYs	HR (95% CIs)
Events	Normal Mucosa	References	Normal Mucosa	References		Model 1	Model 2
All-cause mortality	18,881	32,139	52.67 (51.92–53.42)	46.72 (46.21–47.23)	5.95 (5.04–6.85)	1.53 (1.50–1.56)	1.34 (1.31–1.37)
CVD mortality	3519	7519	9.82 (9.49–10.15)	10.93 (10.68–11.18)	−1.11 (−1.52- −0.71)	1.24 (1.19–1.30)	1.07 (1.02–1.11)
Cancer mortality	7037	10,846	19.63 (19.17–20.09)	15.77 (15.47–16.07)	3.86 (3.32–4.41)	1.70 (1.64–1.75)	1.58 (1.53–1.63)
GI disease mortality	1003	1155	2.80 (2.63–2.98)	1.68 (1.58–1.78)	1.12 (0.92–1.32)	2.37 (2.16–2.60)	1.75 (1.59–1.92)
Other mortality	7322	12,619	20.42 (19.96–20.90)	18.34 (18.03–18.67)	2.08 (1.51–2.65)	1.43 (1.39–1.48)	1.23 (1.19–1.27)

Notes: Model 1: conditioned on family and adjusted for birth year, gender, and calendar period. Model 2: further adjusted for country of birth, educational attainment, number of health care visits, Charlson comorbidity index, and history of GI diseases.

Abbreviations: CIs, confidence intervals; CVD, cardiovascular disease; GI, gastrointestinal; HR, hazard ratio; PYs, Person-years.