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Original Investigation | Gastroenterology and Hepatology
Thirty-Year Incidence and Mortality Trends in Upper and Lower Gastrointestinal
Bleeding in Finland
Pareen Vora, MSc; Arto Pietila, MSc; Markku Peltonen, PhD; Gunnar Brobert, PhD; Veikko Salomaa, MD, PhD
Abstract
IMPORTANCE Epidemiological data on lower gastrointestinal bleeding (GIB) in the general
population are sparse.
OBJECTIVE To describe the incidence, recurrence, mortality, and case fatality rates of major upper
GIB and lower GIB in the general population of Finland between 1987 and 2016.
DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study used data from the 1987 to
the 2012 cycles of the National FINRISK Study, a health examination survey that was conducted every
5 years in Finland. Survey participants were adults aged 25 to 74 years who were recruited from a
population register by random sampling; those with a history of hospitalization for GIB were
excluded. Participants were followed up from survey enrollment to onset of GIB that led to
hospitalization, death from any cause, or study end (December 31, 2016). Follow-up was performed
through linkage with national electronic health registers. Data were analyzed from February 1, 2019,
to January 31, 2020.
MAIN OUTCOMES AND MEASURES Incidence, recurrence, mortality, and case fatality rates for all,
upper, lower, and unspecified GIB. Outcome measures were stratified by sex and age group.
RESULTS Among the 39054 participants included in the study, 494 (1.3%) experienced upper GIB
(321 men [65.0%]; mean [SD] age, 52.8 [12.1] years) and 645 (1.7%) had lower GIB (371 men [57.5%];
mean [SD] age, 54.0 [11.7] years). The age-standardized incidence rate was 0.94 per 1000 person-
years (95% CI, 0.85-1.04) for upper GIB and 1.26 per 1000 person-years (95% CI, 1.15-1.38) for lower
GIB; the incidence was higher in men than in women. Between 1987 and 2016 the incidence rate of
upper GIB remained mostly stable, ranging from 0.40 to 0.66 per 1000 person-years, whereas
constant increases occurred in the incidence of lower GIB until the rate stabilized. The proportion of
recurrent GIB events showed an increasing trend from 1987 to 2016. The upper GIB–specific
mortality was higher (0.07 per 1000 person-years; 95% CI, 0.04-0.09) than the lower GIB–specific
mortality (0.01 per 1000 person-years; 95% CI, 0.001-0.03). Case fatality was high for those with
upper GIB (7.0%; 95% CI, 4.7-10.1) compared with those with lower GIB (0.4%; 95% CI, 0.1-1.3). Case
fatality remained stable over the years but was higher in men (between 5% and 10%) than women
(<2%) with GIB.
CONCLUSIONS AND RELEVANCE This study found that the overall incidence rate of upper GIB was
lower than the incidence of lower GIB, but the recurrence, mortality, and 28-day case fatality were
higher in participants with upper GIB. These data can serve as a reference when putting into context
the rates of drug-associated GIB and can inform efforts to improve GIB care and outcome and to
prevent rebleeding or death for patients with major GIB.
JAMA Network Open. 2020;3(10):e2020172.doi:10.1001/jamanetworkopen.2020.20172
Key Points
Question What are the incidence and
mortality rates and trends in major
upper and lower gastrointestinal
bleeding (GIB) in Finland from 1987
to 2016?
Findings In this cohort study of 39 054
Finnish survey participants, the
age-standardized incidence rate of
major upper GIB was lower than the rate
of lower GIB. Mortality rate and case
fatality were higher in participants with
upper GIB compared with lower GIB.
Meaning Results of this study suggest
that the outcome for GIB did not seem
to improve over the years and that the
incidence, recurrence, and mortality
data can inform efforts to improve care
and prevent rebleeding or death for
patients with major GIB.
+Supplemental content
Author affiliations and article information are
listed at the end of this article.
Open Access. This is an open access article distributed under the terms of the CC-BY-NC-ND License.
JAMA Network Open. 2020;3(10):e2020172.doi:10.1001/jamanetworkopen.2020.20172 (Reprinted) October 9, 2020 1/11
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Introduction
Gastrointestinal bleeding (GIB) is an acute and potentially life-threatening event. Although GIB can
usually be treated successfully, it represents a substantial socioeconomic burden and has a huge
impact at the patient level, including hemodynamic instability, vomiting, abdominal pain, or
discomfort, all of which affect daily functioning.
1
In 2006 in the United States, the hospitalization
rate associated with GIB was 375 per 100 000 people and the in-hospital mortality was 5 per
100 000 people.
2
In the United Kingdom, the total annual cost of hospitalizations associated with
acute upper GIB and its treatment was estimated to be approximately £−
−155.5 million (approximately
US $207.6 million).
3
Individuals at high risk of GIB include those with peptic ulcers, inflammation in
the gastrointestinal tract, liver cirrhosis, or polyps or tumors in the digestive tract as well as those
who use blood-thinning medications or nonsteroidal anti-inflammatory drugs.
4
Although many
studies have reported the occurrence of GIB in cohorts of patients with certain prescribed
medications,
5-9
most studies have focused on upper GIB. Lower GIB is common, but data on lower
GIB are sparse. Few studies have examined the temporal trends of GIB in the general population, and
most of the available data are limited to North America
1,2,10
and Southern Europe.
11-13
Data from the
general population in the Nordic region are lacking. In conducting the present cohort study, we aimed
to describe the incidence, recurrence, mortality, and case fatality rates of major upper and lower GIB
in the general population of Finland between 1987 and 2016.
Methods
The National FINRISK Study surveys were approved by the ethical committee of the Finnish Institute
of Health and Welfare and the Coordinating Ethical Committee of Helsinki and Uusimaa Hospital
District in Finland. Informed consent for all participants was obtained at the beginning of the FINRISK
surveys. Study participants were pseudonymized, and the secondary use of the survey data in the
present observational prospective cohort study was approved by the Finnish Institute of Health and
Welfare in 2017. We followed the Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE) reporting guideline.
14
Study Design and Study Population
This cohort study used data from participants in the FINRISK health examination surveys in Finland.
15
Briefly, FINRISK, which followed the EHES (European Health Examination Survey)
16
and the MONICA
(Monitoring of Trends and Determinants in Cardiovascular Disease)
17
project protocols, was a large
population-based, cross-sectional study on risk factors of chronic, noncommunicable diseases. In
each survey, a random and representative sample of the population was invited from several
geographic regions of Finland, and those who responded to the invitation were enrolled. Initiated in
1972, the FINRISK surveys were carried out every 5 years, with a cohort size of 6000 to 8800 per
survey.
15
Participants were stratified into cohorts that contained at least 250 people of each sex and
each 10-year age group from each geographical area.
15
The participation rate in the 1972 survey was
approximately 90% but gradually decreased over time to approximately 50% in 2012.
15
We included data from the 1987 to 2012 FINRISK survey cohorts. A total of 39 438 unique
participants aged 25 to 74 years were enrolled in the surveys during these periods. Of these
participants, 384 were excluded because they had a history of hospitalization for GIB at baseline,
resulting in a cohort size of 39 054 individuals. Baseline characteristics, including age, sex, marital
status, educational level, occupation, and geographical area, were ascertained at enrollment. To
identify incident cases of GIB, we followed up the participants using record linkage to the nationwide
electronic health registers, which included the hospital discharge register and causes of death
register. These national registers cover virtually all persons living in Finland. The follow-up period was
from the date of enrollment in the survey (when the health examination was conducted) to the onset
JAMA Network Open | Gastroenterology and Hepatology Thirty-Year Incidence and Mortality Trends in Gastrointestinal Bleeding in Finland
JAMA Network Open. 2020;3(10):e2020172.doi:10.1001/jamanetworkopen.2020.20172 (Reprinted) October 9, 2020 2/11
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of GIB that led to hospitalization, death from any cause, or end of the follow-up period (December 31,
2016), whichever occurred first.
We further subdivided the cohort into participants with incident GIB and those without incident
GIB. Cases of GIB were stratified into upper, lower, or unspecified GIB using International
Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases
and Related Health Problems, Tenth Revision (ICD-10) codes. The list of ICD-9 and ICD-10 codes for
upper, lower, and unspecified GIB is available in eTable 1 in the Supplement. A participant could have
experienced GIB at more than 1 site, and a separate follow-up was conducted for each type of GIB
(upper, lower, and unspecified). Incidents of major GIB were defined as GIB that led to hospitalization
or GIB-specific death and were identified from the hospital discharge register and causes of death
register using ICD-9 and ICD-10 codes. These events were either the main or the top 3 contributing
factors in hospitalization or the underlying, direct, or contributing causes of death. Gastrointestinal
bleeding was considered unspecified when the location of the bleeding was not recorded or could
not be identified, and therefore the ICD-9 or ICD-10 code used was unspecified GIB. Recurrent GIB
was identified from incident GIB until death or the end of the follow-up period, and the diagnoses had
to be more than 30 days apart. The recurring GIB had to be of the same type as the incident GIB; that
is, the event was considered recurrent if an individual with incident upper GIB experienced another
upper GIB, if an individual with incident lower GIB experienced another lower GIB, or if an individual
with incident unspecified GIB experienced any other type of GIB at any site.
Statistical Analysis
We calculated incidence rates, recurrence rates, and GIB-specific mortality rates of all GIB, upper GIB,
lower GIB, and unspecified GIB as the number of events divided by the person-time at risk. Case
fatality was calculated as the number of deaths from GIB within 28 days of experiencing a GIB event
divided by the number of individuals with incident GIB during the follow-up. Baseline age was used to
calculate the person-time at risk and to stratify participants into different age groups (eg, 24-29,
30-39, 40-49 years and so on) to ascertain the age-specific rates. Age standardization was
conducted using the European standard population weights.
18
Incidence and mortality rates were
reported per 1000 person-years, and case fatality was reported as a percentage. These outcome
measures were further stratified by participant sex, age group (when possible), and GIB type (upper,
lower, or unspecified).
The 95% CIs for rates were calculated using the Byar method for 10 or more events and the
exact method for fewer than 10 events, and for proportions were calculated using the Wilson Score
method.
19-21
Time trends in incidence rates were calculated for every 5-year period of the FINRISK
surveys from 1987 to 2012 (ie, 1987-1991, 1992-1996, 1997-2001, 2002-2006, 2007-2011, and
2012-2016), and these survey cohorts were followed up from enrollment to the fifth year of the study
period. Time trends in recurrence rate were calculated as the number of recurrent GIB events divided
by the total number of GIB events within each of the 5-year periods from 1987 to 2016. Time trends
in case fatality were calculated as the proportions for each of the 5-year periods from 1987 to 2016.
The difference in the absolute numbers between upper GIB and lower GIB was calculated for each
of the 5-year periods from 1987 to 2016.
All statistical calculations and plots were done with R, version 3.6.1 (R Foundation for Statistical
Computing). Data were analyzed from February 1, 2019, to January 31, 2020.
Results
Study Population and Characteristics
The study included 39 054 participants, who contributed 627 516 person-years of follow-up for a
median duration of 14.9 years. Of these participants, 1081 (2.8%) experienced a major GIB event,
with 494 (1.3%) having upper GIB, 645 (1.7%) having lower GIB, and 135 (0.3%) having unspecified
GIB, whereas 37 973 individuals (97.2%) did not experience GIB. The mean (SD) baseline age was
JAMA Network Open | Gastroenterology and Hepatology Thirty-Year Incidence and Mortality Trends in Gastrointestinal Bleeding in Finland
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53.4 (11.9) years for all participants with incident GIB cases and 47.2 (13.2) years for those with no GIB.
The participants with lower GIB and unspecified GIB were slightly older (mean [SD] age, 54.0 [11.7]
years and 54.9 [11.0] years) than those experiencing upper GIB (52.8 [12.1] years), but all GIB groups
were composed predominantly of male participants (upper: 65.0% men [n = 321]; lower: 57.5%
[n = (371]; unspecified: 61.5% [n = 83]). The proportion of men among the participants experiencing
GIB was 59.9% (n = 648) and among those without GIB was 47.5% (n = 18 026), whereas the
proportions of women were 40.1% (n = 433) and 52.5% (n = 19 947), respectively. The baseline
characteristics of participants are presented in eTable 2 in the Supplement.
Incidence of Major GIB
During the entire study period (1987-2016), the overall crude incidence rate of GIB was 1.74 per 1000
person-years (95% CI, 1.64-1.85) and the overall age-standardized rate was 2.10 per 1000 person-
years (95% CI, 1.96-2.25). When stratified by sex, the overall age-standardized rate was higher in men
than in women (2.62 per 1000 person-years [95% CI, 2.40-2.86] vs 1.62 per 1000 person-years
[95% CI, 1.45-1.81]). Furthermore, when stratified by the site of GIB, the incidence rate was highest
for participants with lower GIB (1.26 per 1000 person-years; 95% CI, 1.15-1.38), followed by those
with upper GIB (0.94 per 1000 person-years; 95% CI, 0.85-1.04) and those with unspecified GIB
(0.26 per 1000 person-years; 95% CI, 0.22-0.32). The age-standardized rates for upper GIB and
lower GIB were higher in men (upper: 1.27 per 1000 person-years [95% CI, 1.12-1.4 4]; lower: 1.50 per
1000 person-years [95% CI, 1.34-1.68]) than in women (upper: 0.64 per 1000 person-years [95%
CI, 0.54-0.76]; lower: 1.04 per 1000 person-years [95% CI, 0.90-1.20]). For unspecified GIB, no
difference was observed between the sexes (men: 0.33 per 1000 person-years [95% CI, 0.26-0.41]
vs women: 0.21 per 1000 person-years [95% CI, 0.15-0.28]) (Table 1).
Table 1. Incidence Rates of GastrointestinalBleeding per 1000 Person-Years Between 1987and 2016
Variable
Upper GIB Lower GIB Unspecified GIB
No. of
cases Person-years
Incidence rate
(95% CI)
No. of
cases Person-years
Incidence rate
(95% CI)
No. of
cases Person-years
Incidence rate
(95% CI)
Men
Overall crude rate 321 290 385.05 1.11 (0.99-1.23) 371 289 976.25 1.28 (1.15-1.42) 83 291 719.25 0.28 (0.23-0.35)
Age-standardized rate NA NA 1.27 (1.12-1.44) NA NA 1.50 (1.34-1.68) NA NA 0.33 (0.26-0.41)
Age-specific rate
24-29 y 18 36 649.38 0.49 (0.29-0.78) 13 36 668.43 0.35 (0.19-0.61) 2 36 754.04 0.05 (0.01-0.20)
30-39 y 40 69 205.99 0.58 (0.41-0.79) 38 69 250.23 0.55 (0.39-0.75) 5 69 459.11 0.07 (0.02-0.17)
40-49 y 68 72 365.87 0.94 (0.73-1.19) 79 72 134.78 1.10 (0.87-1.36) 15 72 662.50 0.21 (0.12-0.34)
50-59 y 97 65 343.17 1.48 (1.20-1.81) 119 65 258.41 1.82 (1.51-2.18) 34 65 706.76 0.52 (0.36-0.72)
60-69 y 75 39 129.32 1.92 (1.51-2.40) 94 38 974.14 2.41 (1.95-2.95) 22 39 366.73 0.56 (0.35-0.85)
70-74 y
a
23 7691.90 2.99 (1.89-4.49) 28 7690.26 3.64 (2.42-5.26) 5 7770.16 0.64 (0.21-1.50)
Women
Overall crude rate 173 334 257.16 0.52 (0.44-0.60) 274 333 797.99 0.82 (0.73-0.92) 52 335 252.34 0.16 (0.12-0.20)
Age-standardized rate NA NA 0.64 (0.54-0.76) NA NA 1.04 (0.90-1.20) NA NA 0.21 (0.15-0.28)
Age-specific rate
24-29 y 9 46 464.70 0.19 (0.09-0.37) 11 46 438.67 0.24 (0.12-0.42) 1 46 525.64 0.02 (0.001-0.12)
30-39 y 19 81 689.35 0.23 (0.14-0.36) 24 81 674.01 0.29 (0.19-0.44) 6 81 814.23 0.07 (0.03-0.16)
40-49 y 35 81 552.84 0.43 (0.30-0.60) 50 81 514.08 0.61 (0.46-0.81) 13 81 798.41 0.16 (0.08-0.27)
50-59 y 52 75 957.69 0.68 (0.51-0.90) 96 75 695.07 1.27 (1.03-1.55) 12 76 252.48 0.16 (0.08-0.27)
60-69 y 46 41 490.36 1.11 (0.81-1.48) 71 41 380.43 1.72 (1.34-2.16) 15 41 720.87 0.36 (0.20-0.59)
70-74 y
a
12 7102.26 1.69 (0.87-2.95) 22 7095.74 3.10 (1.94-4.69) 5 7140.73 0.70 (0.23-1.63)
Total
Crude rate 494 624 642.87 0.79 (0.72-0.86) 645 623 774.23 1.03 (0.96-1.12) 135 626 971.69 0.22 (0.18-0.26)
Age-standardized NA NA 0.94 (0.85-1.04) NA NA 1.26 (1.15-1.38) NA NA 0.26 (0.22-0.32)
Abbreviations: GIB, gastrointestinal bleeding; NA, not applicable.
a
Recruitment of FINRISK survey participants aged 70 to 74 years mainly started in 1997.
JAMA Network Open | Gastroenterology and Hepatology Thirty-Year Incidence and Mortality Trends in Gastrointestinal Bleeding in Finland
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We found that a total of 102 upper GIB events and 108 lower GIB events occurred in the study
participants after restricting each FINRISK cohort (1987-2012) from enrollment to 5 years of
follow-up to obtain incidence rates for each of the 5-year periods from 1987 to 2016. Trends over the
years showed that the incidence of upper GIB remained stable over the past 30 years between 0.40
and 0.66 per 1000 person-years, except for a slight increase to 0.95 per 1000 person-years that
occurred in the 1997 to 2001 period (Figure 1). For lower GIB, the incidence constantly increased
from 0.06 per 1000 person-years in the 1987 to 1991 period to 1.12 per 1000 person-years in the
2002 to 2006 period. Since then, the incidence rate of lower GIB has decreased by almost half (0.54
per 1000 person-years), has become stable in the past decade, and is similar to the upper GIB
incidence rate (0.45 per 1000 person years; 95% CI, 0.24-0.77) (Figure 1). The difference in the
absolute number of events between upper GIB and lower GIB was that the number of upper GIB
events was higher than lower GIB (118 vs 92) until the 1997 to 2001 period. Since then, the number
of lower GIB events has increased substantially and remained high until the end of follow-up on
December 31, 2016 (eFigure in the Supplement).
Recurrence of Major GIB
We found a total of 60 recurrent upper GIB events in patients with an incident upper GIB, 49
recurrent lower GIB events in patients with an incident lower GIB, and 26 recurrent GIB events in
patients with an incident unspecified GIB. The estimated recurrence rate of unspecified GIB was the
highest (71.5 per 1000 person-years; 95% CI, 40.2-113.5), but the absolute number of cases was low
(n = 26). The recurrence rate for upper GIB was higher (22.4 per 1000 person-years; 95% CI,
Figure 1. Incidence Rate Trends in Major Upper and Lower
Gastrointestinal Bleeding (GIB) for 5-Year Cohorts
2.0
1.6
1.2
1.8
1.4
1.0
0.8
0.4
0.6
0.2
0
Incidence rate per 1000 person-years
5-Year survey cohort
2012-
2016
1987-
1991
1992-
1996
1997-
2001
2002-
2006
2007-
2011
Lower GIB
Upper GIB
Error bars indicate 95% CIs.
Table 2. Recurrence Rates of GastrointestinalBleeding per 1000 Person-Years Between1987 and 2016
Variable
Incident upper GIB Incident lower GIB Incident unspecified GIB
No. of
cases Person-years
Recurrence rate
(95% CI)
No. of
cases Person-years
Recurrence rate
(95% CI)
No. of
cases Person-years
Recurrence rate of
any GIB (95% CI)
Men
Overall crude rate 39 1460.0 26.7 (19.0-36.5) 29 1918.7 15.1 (10.1-21.7) 16 244.1 65.6 (37.5-106.5)
Age-standardized rate NA NA 26.0 (18.4-35.7) NA NA 13.8 (8.9-20.2) NA NA 76.1 (34.9-136.0)
Women
Overall crude rate 21 1125.8 18.7 (11.5-28.5) 20 1573.0 12.7 (7.8-19.6) 10 191.6 52.2 (25.0-96.0)
Age-standardized rate NA NA 18.6 (11.0-29.2) NA NA 11.2 (6.4-17.9) NA NA 72.3 (27.5-144.4)
Total
Crude rate 60 2585.7 23.2 (17.7-29.9) 49 3491.7 14.0 (10.4-18.6) 26 435.7 59.7 (39.0-87.4)
Age-standardized rate NA NA 22.4 (16.9-29.0) NA NA 12.3 (8.9-16.6) NA NA 71.5 (40.2-113.5)
Abbreviations: GIB, gastrointestinal bleeding; NA, not applicable.
JAMA Network Open | Gastroenterology and Hepatology Thirty-Year Incidence and Mortality Trends in Gastrointestinal Bleeding in Finland
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16.9-29.0) than the recurrence rate for lower GIB (12.3 per 1000 person-years; 95% CI, 8.9-16.6).
When stratified by sex, the recurrence rate for upper GIB was higher in men than in women, and no
difference in recurrence rate was observed for lower GIB (Table 2). The proportions of recurrent
events calculated over the 5-year survey cohorts from 1987 to 2012 tended to increase over time
(Figure 2). After an incident upper GIB, 73.3% of recurrent upper GIB events (n = 44 of 60) occurred
within 1 year and 88.3% of recurrent upper GIB events (n = 53 of 60) took place within 3 years, with
a median (interquartile range [IQR]) follow-up of 3 (1-16) months. After an incident lower GIB event,
79.6% of recurrent lower GIB events (n = 39 of 49) occurred within 1 year and 91.8% of recurrent
lower GIB events (n = 45 of 49) occurred within 3 years, with a median (IQR) follow-up of 2.5 (1-6)
months.
GIB-Specific Mortality and 28-Day Case Fatality
We observed 57 deaths associated with GIB during the entire study period, of which 38 (66.7%) were
attributed to upper GIB, 4 (7.0%) attributed to lower GIB, and 15 (26.3%) attributed to unspecified
GIB. The overall age-standardized GIB-specific mortality rate was 0.11 per 1000 person-years (95%
CI, 0.08-0.14), 0.18 per 1000 person-years (95% CI, 0.13-0.24) in men, and 0.04 per 1000 person-
years (95% CI, 0.02-0.08) in women. The upper GIB–specific mortality rate was 0.07 per 1000
person-years (95% CI, 0.04-0.09), the lower GIB–specific mortality rate was 0.01 per 1000 person-
years (95% CI, 0.001-0.03), and the unspecified GIB–specific mortality rate was 0.03 per 1000
person-years (95% CI, 0.02-0.05). Upper GIB–specific mortality rates were higher in men than in
women (0.11 per 1000 person-years [95% CI, 0.07-0.16] vs 0.03 per 1000 person-years [95% CI,
0.04-0.09]) (eTable 3 in the Supplement).
After restricting the follow-up to 5 years, we found a total of 13 GIB-specific deaths of
participants. A maximum of 1 to 3 deaths occurred in each of the 5-year periods from 1987 to 2016.
The numbers were too low to enable us to calculate reliable estimates for trends over time.
Forty-nine of the 57 total deaths (86.0%) occurred within 28 days of GIB diagnosis; of these 49
deaths, 34 were from upper GIB, 3 were from lower GIB, and 12 were from unspecified GIB. The
overall age-standardized case fatality during the study period was 4.7% (95% CI, 3.3-6.3). When
stratified by sex, the case fatality was 6.5% (95% CI, 4.5-9.0) in men and 1.8% (95% CI, 0.7-3.6) in
women. The age-standardized case fatality was 7.0% (95% CI, 4.7-10.1) in participants with upper
GIB, 0.4% (95% CI, 0.1-1.3) in participants with lower GIB, and 8.8% (95% CI, 3.9-16.2) in participants
with unspecified GIB (eTable 3 in the Supplement).
Figure 2. Recurrent Major Upper and Lower Gastrointestinal Bleeding
(GIB) for 5-Year Cohorts
30
25
20
10
15
5
0
Recurrence, %
5-Year survey cohort
2012-
2016
1987-
1991
1992-
1996
1997-
2001
2002-
2006
2007-
2011
Recurrent lower GIB
Recurrent upper GIB
Error bars indicate 95% CIs.
JAMA Network Open | Gastroenterology and Hepatology Thirty-Year Incidence and Mortality Trends in Gastrointestinal Bleeding in Finland
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Trends in case fatality for overall GIB among men showed an initial decrease but have remained
constant between 5% and 10%. For women, this case fatality trend was less than 2% in the past 2
decades (Figure 3). The limited number of events did not permit us to perform meaningful analyses
of case fatality stratified by type of GIB.
Discussion
This population-based cohort study from Finland found that the incidence rate of lower GIB was
substantially higher than that of upper GIB, and incidence of upper GIB has remained stable over the
past 30 years. With eradication of Helicobacter pylori, the rate of peptic ulcer bleeding has decreased.
However, upper GIB associated with H pylori composes approximately 15% to 20% of all upper GIB
events; therefore, eradication of H pylori would not substantially alter the trends of overall upper GIB,
which might have been counterbalanced by non-H pylori–associated upper GIB and other risk factors
over the study period.
22
We observed a substantial increase in the incidence of lower GIB until 2006,
which decreased by almost half and then stabilized in the past decade. This trend coincided with a
slight increase in the incidence of colorectal cancer between 1987 and 2016, which was higher in men
than women.
23
Overall, the recurrence rate of upper GIB was twice as high as the recurrence rate of
lower GIB and slightly increased over the years. Further research into the potential factors associated
with the increasing trends is required. Case fatality from GIB remained stable during most of the
follow-up period, with higher case fatality in men than in women. Overall, the incidence and fatality
associated with GIB improved from the earlier FINRISK survey periods that we analyzed. In the later
surveys, however, these rates became stable, and no further improvement was observed.
A recent study in New Zealand that analyzed data from 2002 to 2015 of a population with
predominantly European ancestry reported that the incidence rate of nonfatal GIB was 2.19 per 1000
person-years, which was similar to findings in the present study.
24
A review of studies from Europe
on acute upper GIB that used data from the 1990s reported that the incidence rate of acute upper
GIB ranged from 0.36 to 1.72 per 1000 person-years,
13
which was within or higher than the range
shown in the present study. Compared with the present study, the incidence rates of upper GIB in the
United States (from 1998 to 2006) were higher at between 1.46 and 1.70 per 1000 person-years and
were comparable to those of Spain (from 1996 to 2005), which ranged from 0.47 to 0.87 per 1000
person-years.
2,12
Furthermore, similar to the present study, these studies showed decreased or stable
incidence of upper GIB over the years, a higher incidence in men than in women, and increased
Figure 3. Twenty-Eight-Day Case Fatality Trends in Major Gastrointestinal
Bleeding for 5-Year Cohorts
90
70
50
80
60
40
30
10
0
20
28-d case fatality, %
5-Year survey cohort
2012-
2016
1987-
1991
1992-
1996
1997-
2001
2002-
2006
2007-
2011
Women
Men
Error bars indicate 95% CIs.
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incidence with age.
2,11-13,25,26
Few studies that reported the incidence of lower GIB in the general
population showed that the rates in the United States (1998-2006), Spain (1996-2005), and Italy
(2001-2010) were about half of the rate reported in our study.
10-12
Similar to this study, previous
studies
10-12
reported a slight increasing trend in the incidence of lower GIB or complications. Unlike
other studies, the present study showed that the incidence of lower GIB was significantly higher in
men than in women.
10-12
The proportion of recurrent upper GIB in the present study was within the range of a previous
review (between 7% and 16%).
13
Another review (1994-2003) on lower GIB reported that the
recurrent lower GIB ranged from 10% to 40%, which was higher than observed in this study.
27
The
study from Spain reported that the mortality rates of GIB decreased over time, and several studies in
the United States also reported decreasing mortality for upper GIB.
10,12,28,29
However, this trend
could not be calculated in this study because of the low number of cases. Overall mortality rates of
lower GIB were lower in the present study than in the review of studies in 2005.
27
Improved health
care and early detection or diagnosis of bleeding are likely to be associated with the decreased
mortality of GIB.
28,29
Compared with the study from New Zealand,
24
the 28-day case fatality for
overall GIB was 2 times higher in our study. In addition, the trend in case fatality of GIB decreased
sharply in the early years of the FINRISK surveys and remained stable in recent decades, and the case
fatality range was similar to the ranges in the studies from Spain and the United States.
10,12
We believe that the findings of this study will be useful in clinical practice. Specifically, the data
can inform efforts to improve the care and outcomes for patients with GIB, especially lower GIB, and
to prevent recurrent bleeding or death in patients with upper GIB. Incidence, recurrence, mortality,
and case fatality rates of GIB in the general population are useful to know when putting into context
the rates of drug-associated GIB.
Strengths and Limitations
This study has some strengths. It had a population-based design, a large sample size that was
representative of the general population in Finland, and minimal or no participant loss to follow-up.
The long-term follow-up of 30 years enabled the analysis of temporal trends of GIB over the past 3
decades, which covered changes in both characteristics of the general population and medical
practice. Studies of the trends of GIB in the general population in Europe and in Asia are needed,
especially for lower GIB for which research data are sparse. Upper GIB has been extensively studied,
but the data on trends in the general populations of Asia and Europe may be limited and warrant
further investigation. In addition, the risk factors associated with the changes in trends need to be
ascertained to identify the areas for improvement.
This study also has some limitations. The electronic health register data were originally collected
for administrative purposes. Accordingly, some misclassification in recording the GIB diagnoses and
causes of death may have occurred; however, the magnitude of such errors is likely to be small
compared with the large number of events. The number of deaths from GIB was low, and therefore
the mortality and case fatality estimates had wide CIs. Diagnostic accuracy and coding accuracy have
improved over time. Therefore, the time trends, especially the early rates, must be interpreted with
caution. Participation in the FINRISK surveys declined over the years, and the nonparticipants were
more likely to be young, to be male, to have lower socioeconomic status, and to have more chronic
illnesses, which could lead to the underrepresentation of this group, especially in later surveys.
30
Recruitment of FINRISK survey participants aged 70 to 74 years mainly started in a few geographic
areas in 1997, and hence the rates for this age group should be interpreted with caution.
Conclusions
This study analyzed the epidemiological data of major upper and lower GIB in a large representative
sample of the general population in Finland. The incidence of upper GIB remained stable, whereas
the incidence of lower GIB showed an increase over the years. Even though the overall incidence rate
JAMA Network Open | Gastroenterology and Hepatology Thirty-Year Incidence and Mortality Trends in Gastrointestinal Bleeding in Finland
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of upper GIB was lower than that of lower GIB, the recurrence and mortality rates were higher in
participants with upper GIB. The case fatality of all GIB remained stable in the past 2 decades. Thus,
the outcomes did not seem to have improved despite more accurate diagnostic methods and likely
earlier detection. The data presented here can serve as a reference for improving the care and
outcome for patients with major GIB and for preventing rebleeding or death in these patients.
ARTICLE INFORMATION
Accepted for Publication: July 30, 2020.
Published: October 9, 2020. doi:10.1001/jamanetworkopen.2020.20172
Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License.©2020Vora
Petal.JAMA Network Open.
Corresponding Author: Pareen Vora, MSc, Bayer AG, Muellerstrasse 178, 13353 Berlin, Germany (pareen.vora@
bayer.com).
Author Affiliations: Epidemiology, BayerAG, Berlin, Germany (Vora); Institute for Medical Information Processing,
Biometry, and Epidemiology, Ludwig Maximilians Universität Munich, Munich, Germany (Vora); Pettenkofer
School of Public Health, Munich, Germany (Vora); Department of Public Health Solutions, Finnish Institute for
Health and Welfare (THL), Helsinki, Finland (Pietila, Peltonen, Salomaa); Medical Affairs, Bayer AB, Stockholm,
Sweden (Brobert).
Author Contributions: Dr Salomaa and Mr Pietila had full access to all of the data in the study and take
responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Vora, Brobert, Salomaa.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Vora, Brobert.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Vora, Pietila, Peltonen, Brobert.
Obtained funding: Vora, Brobert, Salomaa.
Administrative, technical, or material support: Brobert, Salomaa.
Supervision: Brobert, Salomaa.
Conflict of Interest Disclosures: Mr Vora reported being an employee of Bayer AG. Mr Pietila reported being an
employee of the Finnish Institute for Health and Welfare,which received a grant from Bayer AG during the conduct
of the study. Dr Peltonenrepor ted beingan employee of the Finnish Institute for Health and Welfare. Dr Brobert
reported being an employee of Bayer AB. Dr Salomaa reported being an employee of the Finnish Institute for
Health and Welfare, which received a grant from Bayer AGduring the conduc t of the study, as well as receiving
personal fees from Novo Nordisk and honorarium for consultation from Sanofi outside the submitted work. No
other disclosures were reported.
Funding/Support: This study was funded in part by Bayer AG. Dr Salomaa was supported by the Finnish
Foundation for Cardiovascular Research.
Role of the Funder/Sponsor:The funders had no role in the design and conduc t of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approvalof the manuscript; and
decision to submit the manuscript for publication.
Meeting Presentation: The preliminary results of this study were presented as 2 posters at the 27th United
European Gastroenterology Week Congress, October 21 and 22, 2019, Barcelona, Spain.
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SUPPLEMENT.
eTable 1. List of ICD 9 and ICD 10 Codes for GastrointestinalBleeding s
eTable 2. Baseline Characteristics of the Study Participants by Type of Gastrointestinal Bleeding During Follow-up
eFigure. Absolute Difference Between the Number of Upper and Lower Gastrointestinal Bleeding Events for
Five-Year Period Each
eTable 3. Mortality Rates and 28-Day Case-Fatality Due to Gastrointestinal Bleedings Between 1987 and 2016
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