Primary and Secondary Prevention of Diverticular Disease
Walid.H. AldooriWyeth Consumer Healthcare Inc.CANADA
Falk Symposium
Diverticular Disease: Emerging Evidence in a Common Condition
Munich, June 17-18,2005
Outline• Introduction
• Health Professionals Follow-Up Study
• Dietary Factors
• Non-Dietary Factors
• Gaps in our knowledge
• Can we reduce the risk of Diverticular Disease ?
Introduction
• Diverticular disease (DD)is one of the most common disorders of the colon in Western societies.
• It is suggested that lifestyle factors can explain the increase in the prevalence of DD.
• Identifying these factors is important in the prevention of DD and/or the complications of DD.
Burkitt and Painter’s Dietary Fiber Hypothesis
• Three decades have passed since this hypothesis was widely publicized
• Several studies have investigated dietary and non-dietary factors and the risk of DD
• Almost all the studies were either case-control studies which are more prone to bias or did not control for potential confounding variables
Health Professionals Follow-up Study (HPFS)
• To minimize the potential of bias, dietary and non-dietary factors were investigated prospectively among 51,529 health professional US men participating in an ongoing cohort study
• The study began in 1986 when cohort members completed a dietary questionnaire and provided other relevant information
• Follow-up questionnaires every two years and dietary questionnaires every four years
Health Professionals Follow-up Study
47,678 Men
40-75 Years Old 382 cases
1986 1988 1990 1992FUQ FUQ FUQ
Follow-up Time
Baseline Questionnaire
and FFQ
Identification of DD Cases
• After four years of follow-up, 503 newly diagnosed cases of DD were identified
• Of the 503 new cases, 382 were classified as symptomatic ( pain, change of bowel habits, or bleeding)
• To reduce the possibility of detection bias, the symptomatic cases were used as our primary end point
• In 96 percent of the cases, the diverticula were located in the left colon
54321
<0.00001
<0.00001
8.8
61
0.62 (0.45-0.86)
0.61 (0.43-0.87)
5.5
57
0.54 (0.39-.076)
0.60 (0.43-0.85)
3.8
84
0.85 (0.63-1.15)
0.90 (0.66-1.23)
2.3
98
1.03 (0.77-1.38)
1.10 (0.82-1.47)
1.1
85
1.0
1.0
Fruit Fiber (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
<0.00001
0.01
8.3
54
0.48 (0.35-0.67)
0.54 (0.38-0.76)
6.4
72
0.71 (0.52-0.96)
0.78 (0.57-1.06)
5.4
86
0.72 (0.54-0.96)
0.76 (0.57-1.02)
4.5
72
0.78 (0.58-1.06)
0.81 (0.59-1.10)
3.3
101
1.0
1.0
Total Crude Fiber (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.0002
0.01
32.0
55
0.51 (0.37-0.71)
0.58 (0.41-0.83)
24.0
83
0.78 (0.58-1.05)
0.87 (0.64-1.17)
21.0
73
0.73 (0.54-0.99)
0.77 (0.57-1.05)
18.0
75
0.76 (0.57-1.03)
0.79 (0.58-1.07)
13.0
99
1.0
1.0
Total Dietary Fiber (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
P Value for
Trend*
QuintileVariable
TABLE 1: Relative Risk of DD by quintiles of total dietary fiber, crude fiber, and by dietary fiber from fruits, vegetables and cereals
TABLE 1: Relative Risk of DD by quintiles of total dietary fiber, crude fiber, and by dietary fiber from fruits, vegetables and cereals
*Test for trend was calculated by using the median intake of nutrients in each quintile as a continuous variable in a multiple logistic regression.†Adjusted for age and total energy. ‡Adjusted for age, physical activity, and energy-adjusted total fat.( Modified from Aldoori WH, et al. Am J Clin Nutr 1994;60:757-764)
54321
0.23
0.72
13.5
78
1.09 (0.77-1.54)
1.06 (0.76-1.47)
8.2
61
0.85 (0.58-1.24)
0.87 (0.61-1.22)
5.7
78
1.10 (0.79-1.54)
1.08 (0.78-1.49)
3.7
91
1.21 (0.89-1.66)
1.23 (0.90-1.67)
1.7
77
1.0
1.0
Cereal Fiber (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.003
0.003
12.4
54
0.55 (0.37-0.84)
0.59 (0.41-0.86)
8.6
78
0.90 (0.64-1.26)
0.87 (0.63-1.20)
6.6
87
0.98 (0.71-1.35)
1.0 (0.73-1.36)
5.1
82
0.93 (0.68-1.28)
0.96 (0.70-1.31)
3.4
84
1.0
1.0
Vegetable Fiber (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
P Value for
Trend*
QuintileVariable
TABLE 2: Relative Risk of DD by quintiles of soluble and insoluble fiber components
† Adjusted for age and total energy.‡ Adjusted for age, physical activity, and energy-adjusted total fat.(Aldoori WH, et al. J Nutr 1998;128:717-719)
54321
0.001
0.02
22.70
0.55 (0.39-0.78)
0.63 (0.44-0.91)
17.90
0.80 (0.59-1.10)
0.87 (0.63-1.20)
15.20
0.78 (0.57-1.07)
0.80 (0.58-1.10)
13.0
0.89 (0.65-1.22)
0.91 (0.66-1.24)
10.1
1.0
1.0
Insoluble Fiber (g/d)
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.05
0.40
8.60
0.82 (0.59-1.16)
0.90 (0.62-1.29)
9.90
0.83 (0.59-1.17)
0.91 (0.65-1.29)
5.90
1.00 (0.72-1.38)
1.04 (0.75-1.44)
5.10
1.03 (0.75-1.43)
1.05 (0.76-1.45)
4.10
1.0
1.0
Soluble Fiber ( g/d)
RR† (95% CI)
Multivariate RR‡ (95% CI)
P Value for
Trend
QuintileVariable
TABLE 3: Relative Risk of DD by quintiles of hemicellulose, cellulose, and lignin intake
54321
0.0002
0. 01
2.40
0.53 (0.38-0.76)
0.62 (0.43-0.89)
1.80
0.65 (0.47-.090)
0.71 (0.51-1.00)
1.50
0.87 (0.64-1.19)
0.89 (0.65-1.21)
1.20
0.82 (0.60-1.12)
0.83 (0.61-1.14)
1.00
1.0
1.0
Lignin (g/d)
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.0002
0.002
8.00
0.47 (0.33-0.66)
0.52 (0.36-0.75)
6.20
0.78 (0.57-1.06)
0.83 (0.61-1.14)
5.30
0.71 (0.52-0.97)
0.74 (0.54-1.01)
4.40
0.75 (0.55-1.03)
0.76 (0.56-1.05)
3.40
1.0
1.0
Cellulose (g/d)
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.01
0.11
11.70
0.78 (0.56-1.08)
0.88 (0.62-1.25)
8.90
0.78 (0.56-1.09)
0.84 (0.60-1.18)
7.30
0.77 (0.55-1.07)
0.79 (0.56-1.10)
6.00
1.27 (0.94-1.71)
1.29 (0.95-1.74)
4.40
1.0
1.0
Hemicellulose (g/d)
RR† (95% CI)
Multivariate RR‡ (95% CI)
P Value for
Trend
QuintileVariable
†Adjusted for age and total energy.‡Adjusted for age, physical activity, and energy-adjusted total fat.(Aldoori WH, et al. J Nutr 1998;128:717-719)
Fig. 1: Relative Risk* of DD by levels of Calorie-adjusted Dietary Fiber and Red Meat Intake
00.5
11.5
22.5
33.5
Low (<17) Medium (17-28)
High (29+)
Low (<28.5)
Medium (28.6-116.6)
High (>116.6)
*Adjusted for age and total energy.(Aldoori WH, et al. Am J Clin Nutr 1994; 60:757-764)
RED MEAT INTAKE (g/d)
DIETARY FIBRE INTAKE (g/d)
1.96 1.79
1.0
3.162.60
1.90
3.22
2.53
1.73
Rel
ativ
e R
isk
TABLE 4: Relative Risk of DD by quintiles of total fat and specific dietary fats
54321
0.13
0.10
43.0
87
1.28 (0.94-1.76)
1.32 (0.96-1.81)
35.0
70
1.06 (0.76-1.48)
1.08 (0.77-1.51)
30.0
85
1.28 (0.93-1.75)
1.30 (0.94-1.79)
25.0
73
1.06 (0.76-1.47)
1.07 (0.77-1.49)
18.0
70
1.0
1.0
Vegetable Fat (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.12
0.80
52.0
74
1.43 (1.02-2.01)
1.08 (0.75-1.56)
43.0
83
1.57 (1.13-2.19)
1.27 (0.90-1.80)
37.0
80
1.39 (0.99-1.94)
1.20 (0.85-1.69)
31.0
88
1.66 (1.20-2.03)
1.50 (1.08-2.10)
22.0
60
1.0
1.0
Animal Fat (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.005
0.20
82.0
98
1.71 (1.0-2.37)
1.38 (0.96-1.96)
76.0
58
1.25 (0.86-1.83)
1.09 (0.74-1.60)
70.0
100
1.57 (1.13-2.19)
1.40 (1.0-1.98)
60.0
76
1.27 (0.90-1.81)
1.17 (0.82-1.67)
47.0
55
1.0
1.0
Total Fat (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
P for Trend*
QuintileFats
54321
0.19
0.16
17.4
88
1.25 (0.92-1.71)
1.28 (0.94-1.76)
14.6
79
1.14 (0.83-1.57)
1.14 (0.83-1.58)
12.8
66
0.95 (0.68-1.32)
0.95 (0.68-1.32)
11.3
79
1.14 (0.83-1.57)
1.15 (0.83-1.58)
8.6
73
1.0
1.0
Polyunsaturated Fatty Acids (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.01
0.26
31.2
86
1.53 (1.10-2.11)
1.24 (0.87-1.75)
28.6
79
1.41 (1.01-1.97)
1.19 (0.84-1.68)
26.0
86
1.45 (1.04-2.01)
1.29 (0.92-1.81)
22.4
73
1.26 (0.90-1.77)
1.15 (0.81-1.62)
16.5
61
1.0
1.0
Monounsaturated Fatty Acids (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.01
0.47
30.3
82
1.61 (1.16-2.25)
1.22 (0.85-1.76)
26.7
80
1.51 (1.08-2.13)
1.27 (0.89-1.81)
24.3
82
1.54 (1.10-2.15)
1.34 (0.94-1.89)
20.9
82
1.45 (1.04-2.02)
1.30 (0.92-1.83)
15.1
59
1.0
1.0
Saturated Fatty Acids (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
P for Trend*
QuintileFats
TABLE 4: Relative Risk of DD by quintiles of total fat and specific dietary fats
54321
0.002
0.25
4.6
77
1.49 (1.06-2.09)
1.29 (0.91-1.84)
3.7
76
1.70 (1.22-2.37)
1.46 (1.03-2.07)
3.2
106
1.73 (1.27-2.35)
1.52 (1.10-2.10)
2.7
64
1.28 (0.90-1.81)
1.17 (0.82-1.67)
1.9
62
1.0
1.0
Trans Fatty Acids (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
0.20
0.38
0.5
67
0.86 (0.61-1.19)
0.97 (0.69-1.36)
0.3
77
0.92 (0.67-1.27)
1.02 (0.74-1.41)
0.2
83
1.17 (0.86-1.61)
1.25 (0.91-1.71)
0.1
86
1.08 (0.79-1.47)
1.11 (0.81-1.52)
<0.1
72
1.0
1.0
Omega-3 Fatty Acids (median g/d)
Cases
RR† (95% CI)
Multivariate RR‡ (95% CI)
P for Trend*
QuintileFats
*Test for trend was calculated by using the median intake of nutrients in each quintile as a continuous variable in a multiple logistic regression.†Adjusted for age and total energy. ‡Adjusted for age, energy-adjusted dietary fiber and physical activity.(Aldoori WH, et al. Am J Clin Nutr 1994;60:757-764)
TABLE 4: Relative Risk of DD by quintiles of total fat and specific dietary fats
Fig. 2: Relative Risk* of DD by levels of Calorie-adjusted Dietary Fiber and Total Fat Intake
0
0.5
1
1.5
2
2.5
Low (<17) Medium (17-28)
High (+29)
Low (<47) (g/d)
Medium (47-81)
High (>81.1)
*Adjusted for age and total energy.(Aldoori WH, et al. Am J Clin Nutr 1994; 60:757-764)
TOTAL FAT INTAKE (g/d)
TOTAL FIBRE INTAKE (g/d)
1.501.26
1.0
1.881.62
1.14
2.35
1.72
0.86
Rel
ativ
e R
isk
*Adjusted for age, energy-adjusted dietary fiber and energy-adjusted total fat.† Test for trend was calculated by using the median alcohol intake in each category as continuous in a multiple logistic regression.(Aldoori WH, et al. Ann Epidemiol 1995;5:221-228)
TABLE 5: Relative Risk of DD according to alcohol intake
1.38 (0.98-1.95)1.20 (0.86-1.67)6231,3235.1-10.0 g/day
1.36 (0.94-1.97)
(P value for trend†
=0.37)
1.40 (0.95-2.07)
(P value for trend†
=0.15)3814,33630.1+
1.16 (0.81-1.66)1.28 (0.92-1.80)5825,75115.1-30.0 g/day
1.13 (0.77-1.66)1.09 (0.74-1.60)3920,75610.1-15 g/day
1.30 (0.96-1.76)1.28 (0.95-1.71)10851,0070.1-5.0 g/day
ReferenceReference7744,265None
Multivariate*Age adjusted
Relative risk (95% CI)Observed
casesPerson-
yearsAlcohol
*Number of cases do not always add up to 382, because of missing information for specific beverages.** Adjusted for age, energy-adjusted dietary fiber and energy-adjusted total fat. ‡Test for trend was calculated by using the
median intake specific beverages in each category as continuous in a multiple logistic regression.(Aldoori WH, et al. Ann Epidemiol 1995;5:221-228)
TABLE 6: Relative Risk of DD by levels of total caffeine, coffee, tea, and decaffeinated coffee
(P value for trend‡
=0.98)(P value for trend‡
=0.25)
1.11 (0.78-1.57)1.23 (0.87-1.73)7337,388615 mg/day
1.26 (0.91-1.77)1.37 (0.98-1.90)8437,839355 mg/day
1.14 (0.81-1.61)1.23 (0.88-1.71)7637,185165 mg/day
1.34 (0.97-1.86)1.14 (1.01-1.94)8837,48682 mg/day
ReferenceReference6137,5946.0 mg/day
CAFFEINE (median mg/day)
Multivariate**Age adjusted
Relative risk (95% CI)Observed
cases*Person-
yearsVariable
TABLE 6: Relative Risk of DD by levels of total caffeine, coffee, tea, and decaffeinated coffee
(P value for trend‡
=0.81)(P value for trend‡
=0.53)
0.95 (0.65-1.38)1.09 (0.75-1.58)3919,890š4-5/day
1.01 (0.76-1.34)1.09 (0.82-1.45)8942,8132-3/day
1.0 (0.78-1.30)1.05 (0.81-1.35)13565,6721-3/month to 1/day
ReferenceReference10454,696Almost never
COFFEE (cups)
Multivariate**Age adjusted
Relative risk (95% CI)Observed
cases*Person-
yearsVariable
TABLE 6: Relative Risk of DD by levels of total caffeine, coffee, tea, and decaffeinated coffee
(P value for trend‡
=0.12)(P value for trend‡
=0.09)
1.04 (0.42-2.54)1.04 (0.43-2.55)52,718š4-5/day
1.53 (1.04-2.26)1.53 (1.04-2.24)3242,8132-3/day
1.14 (0.91-1.42)1.11 (0.89-1.38)18165,6721-3/month to 1/day
ReferenceReference13876,599Almost never
TEA (cups)
Multivariate**Age adjusted
Relative risk (95% CI)Observed
cases*Person-
yearsVariable
TABLE 6: Relative Risk of DD by levels of total caffeine, coffee, tea, and decaffeinated coffee
(P value for trend‡
=0.17)(P value for trend‡
=0.02)
1.12 (0.62-2.02)1.08 (0.60-1.95)126,456š4-5/day
1.56 (1.13-2.15)1.45 (1.00-1.95)5320,6002-3/day
1.51 (1.20-1.90)1.41 (1.12-1.76)16769,9411-3/month to 1/day
ReferenceReference13384,692Almost never
DECAFFEINATED COFFEE (cups)
Multivariate**Age adjusted
Relative risk (95% CI)Observed
cases*Person-
yearsVariable
54321
0.001
0.01
41.0
0.53 (0.37-0.75)
0.60 (0.41-0.87)
15.0
0.79 (0.61-1.03)
0.88 (0.67-1.15)
3.5
0.74 (0.57-0.97)
0.78 (0.60-1.02)
0
1.0
1.0
Vigorous activity (median of Total MET) 2
RR * (95% CI)
Multivariate RR‡ (95% CI)
0.41
0.65
20.8
0.93 (0.67-1.30)
0.93 (0.67-1.69)
7.6
1.06 (0.77-1.46)
1.09 (0.79-1.49)
3.4
0.78 (0.56-1.10)
0.79 (0.56-1.12)
1.4
1.13 (0.83-1.55)
1.15 (0.84-1.58)
0.1
1.0
1.0
Non-vigorous activity (median of Total MET)§
RR * (95% CI)
Multivariate RR‡ (95% CI)
0.0002
0.008
46.8
0.57 (0.41-0.79)
0.63 (0.45-0.88)
22.6
0.68 (0.50-0.92)
0.74 (0.54-1.01)
11.3
0.67 (0.49-0.91)
0.71 (0.52-0.97)
4.8
0.89 (0.67-1.18)
0.91 (0.68-1.21)
0.9
1.0
1.0
Total physical activity (median of Total MET) ¶
RR* (95% CI)
Multivariate RR‡ (95% CI)
P Value for
Trend †
CategoryVariable
TABLE 7: Relative Risk of DD by physical activity, non-vigorous, and vigorous activity levels
*Adjusted for age. †Test for trend was calculated by using the median Total MET value of exercise in each category as a continuous variable in a multiple logistic regression. ‡Adjusted for age, energy-adjusted dietary fiber and energy-adjusted total fat.§Included flight of stairs climbed and walking or hiking outdoors (including walking at golf).2Included running (10 minutes/mile or faster), jogging (slower than 10 minutes/mile), lap swimming, tennis, squash or racquetball, calisthenics or rowing, bicycling (including stationary machines).¶Total MET = sum of the average time/week spent in each activity x MET value of each activity. MET value = caloric need/kg body wt/hour during activity
caloric need/kg body wt/hour at rest(Aldoori WH, et al. Gut 1995;36:276-282).
0
0.5
1
1.5
2
2.5
3
Low (<17) Medium (17-28)
High (+29)
High (>32.5)
Medium (1-32.5)
Low (<1.0)
Fig. 3: Relative Risk* of DD by levels of Calorie-adjusted Dietary Fiber and Physical Activity
*Adjusted for age and total energy.(Aldoori WH, et al. Gut 1995; 36:276-282)
PHYSICAL ACTIVITY(Total MET)
DIETARY FIBRE INTAKE (g/d)
0.851.21
1.0
1.811.43
0.80
2.56
1.551.20
Rel
ativ
e R
isk
Body Mass Index (BMI)
• There was a positive association between increasing age adjusted BMI and and the risk of DD
• This association was attenuated and non significant when we adjusted for other confounding variables
• Total caloric intake was not associated with risk of DD
TABLE 8: Relative Risk of DD by smoking status
1.28 (0.78-2.11)1.52 (0.93-2.47)185,81015-24 cig/day
(P value for trend‡
=0.36)(P value for trend‡
=0.05)
1.25 (0.75-2.09)1.55 (0.94-2.55)175,34725+ cig/day
0.94 (0.50-1.80)1.03 (0.55-1.96)104,8201-14 cig/day
Current smokers (cig/day)
0.96 (0.77-1.19)0.98 (0.79-1.22)16377,912Past smokers
ReferenceReference15984,506Non-smokers
SMOKING STATUS
Multivariate†Age adjusted
Relative risk (95% CI)Observed
cases*Person-
yearsVariable
* Numbers of cases do not always add up to 382, because of missing information for smoking.† Adjusted for age, energy-adjusted dietary fiber, and energy-adjusted total fat. ‡ Test for trend is calculated by using the median number of cigarettes smoked across categories of current smoking in a multiple logistic regression.(Aldoori WH, et al. Ann Epidemiol 1995;5:221-228).
TABLE 9: Relative risk of DD by NSAIDs and acetaminophen use in the HPFS
0.0040.01P Value
2.24 (1.28 - 3.91)1.50 (1.09 - 2.06)Multivariate RR (95% CI)‡
2.19 (1.28 - 3.76)1.52 (1.11 - 2.08)Age-adjusted RR (95% CI)†
34 / 8, 74545 / 13, 682Users, Cases/person-years*
118 / 51, 475265 / 122, 249Nonusers, Cases/person-years
NSAID§
1.81 (0.79 - 4.11)1.33 (0.88 - 2.03)Multivariate RR (95% CI) ‡
0.160.18P Value
1.82 (0.81 - 4.07)1.40 (0.93 - 2.13)Age-adjusted RR (95% CI)†
19 / 4, 90624 / 7, 840Users, Cases/person-years*
133 / 55,314286 / 128, 091Nonusers, Cases/person-years
Acetaminophen
1990 to 19921988 to 1992Follow-up Period
1988 + 19901988NSAIDs and acetaminophen Use
Variable
*Participants who reported NSAIDs and acetaminophen use (the follow-up period for1988 was 1988-1992; for 1988 and 1990, 1990-1992); nonusers reported no NSAID or acetaminophen use during the specified time periods. †Age-adjusted relative risk and 95% CI for users compared with nonusers of NSAID or acetaminophen for each of the specified time periods. ‡ Relative risk adjusted for age, physical activity, energy-adjusted dietary fiber and total fat. § Does not include aspirin. NSAID indicates nonsteroidal anti-inflammatory drug.(Aldoori WH, et al. Arch Fam Med 1998;7:255-260)
TABLE 10: Relative risk of DD for participants whose main symptoms were abdominal pain and change in bowel habits, by NSAIDs and acetaminophen use in the HPFS.
0.0090.14P Value
2.32 (1.24 - 4.35)1.33 (0.91 - 1.96)Multivariate RR (95% CI)‡
2.27 (1.24 - 4.17)1.35 (0.92 - 1.98)Age-adjusted RR (95% CI)†
24 / 8, 74530 / 13, 682Users, Cases/person-years*
89 / 51,475200 / 122, 249Nonusers, Cases/person-years
NSAID§
1.18 (0.37 - 3.71)1.04 (0.60 -1.79)Multivariate RR (95% CI) ‡
0.780.89P Value
1.17 (0.37 - 3.69)1.09 (0.63 - 1.87)Age-adjusted RR (95% CI)†
11 / 4, 90614 / 7, 840Users, Cases/person-years*
102 / 55,314216 / 128, 091Nonusers, Cases/person-years
Acetaminophen
1990 to 19921988 to 1992Follow-up Period
1988 + 19901988NSAIDs and acetaminophen Use
Variable
*Participants who reported NSAIDs and acetaminophen use (the follow-up period for1988 was 1988-1992; for 1988 and 1990, 1990-1992); nonusers reported no NSAID or acetaminophen use during the specified time periods. †Age-adjusted relative risk and 95% CI for users compared with nonusers of NSAID or acetaminophen for each of the specified time periods. ‡ Relative risk adjusted for age, physical activity, energy-adjusted dietary fiber and total fat. § Does not include aspirin. (Aldoori WH, et al. Arch Fam Med 1998;7:255-260)
TABLE 11: Relative risk of DD for participants whose main symptoms were bleeding, by NSAIDs and acetaminophen use in the HPFS.
0.050.07P Value
4.64 (0.99 - 21.74)2.15 (0.94 - 4.93)Multivariate RR (95% CI)‡
4.20 (1.03 - 17.17)2.23 (0.99 - 4.99)Age-adjusted RR (95% CI)†
5 / 8, 7457 / 13, 682Users, Cases/person-years*
9 / 51,47528 / 122, 249Nonusers, Cases/person-years
NSAID§
13.63 (3.53 - 52.6)3.75 (1.63 - 8.64)Multivariate RR (95% CI) ‡
0.00020.002P Value
14.62 (5.38 - 39.71)4.11 (1.93 - 8.77)Age-adjusted RR (95% CI)†
6 / 4, 9067 / 7, 840Users, Cases/person-years*
8 / 55,31428 / 128, 091Nonusers, Cases/person-years
Acetaminophen
1990 to 19921988 to 1992Follow-up Period
1988 + 19901988NSAIDs and acetaminophen Use
Variable
*Participants who reported NSAIDs and acetaminophen use (the follow-up period for1988 was 1988-1992; for 1988 and 1990, 1990-1992); nonusers reported no NSAID or acetaminophen use during the specified time periods. †Age-adjusted relative risk and 95% CI for users compared with nonusers of NSAID or acetaminophen for each of the specified time periods. ‡ Relative risk adjusted for age, physical activity, energy-adjusted dietary fiber and total fat. § Does not include aspirin. (Aldoori WH, et al. Arch Fam Med 1998;7:255-260)
Gaps in our Knowledge
• Better understanding of the interactions between colonic structures, motility, diet, lifestyle and genetic factors
• Better understanding why symptoms develop
• Better understanding whether specific factors are important for the formation of diverticula, and whether different factors contribute to the symptomatic presentation and / or complications
Can we reduce the risk of DD?
• A diet high in fiber mainly from fruits and vegetables and low in total fat and red meat decreases risk of DD
• Insoluble component of fiber is strongly associated with lower risk of DD. This association was particularly strong for cellulose
Fig. 1: Relative Risk* of DD by levels of Calorie-adjusted Dietary Fiber and Red Meat Intake
00.5
11.5
22.5
33.5
Low (<17) Medium (17-28)
High (29+)
Low (<28.5)
Medium (28.6-116.6)
High (>116.6)
*Adjusted for age and total energy.(Aldoori WH, et al. Am J Clin Nutr 1994; 60:757-764)
RED MEAT INTAKE (g/d)
DIETARY FIBRE INTAKE (g/d)
1.96 1.79
1.0
3.162.60
1.90
3.22
2.53
1.73
Rel
ativ
e R
isk
Fig. 2: Relative Risk* of DD by levels of Calorie-adjusted Dietary Fiber and Total Fat Intake
0
0.5
1
1.5
2
2.5
Low (<17) Medium (17-28)
High (+29)
Low (<47) (g/d)
Medium (47-81)
High (>81.1)
*Adjusted for age and total energy.(Aldoori WH, et al. Am J Clin Nutr 1994; 60:757-764)
TOTAL FAT INTAKE (g/d)
TOTAL FIBRE INTAKE (g/d)
1.501.26
1.0
1.881.62
1.14
2.35
1.72
0.86
Rel
ativ
e R
isk
• Caffeine, smoking and alcohol do not substantially increase risk of DD, nor does obesity
• Higher levels of physical activity seem to reduce risk of DD
0
0.5
1
1.5
2
2.5
3
Low (<17) Medium (17-28)
High (+29)
High (>32.5)
Medium (1-32.5)
Low (<1.0)
Fig. 3: Relative Risk* of DD by levels of Calorie-adjusted Dietary Fiber and Physical Activity
*Adjusted for age and total energy.(Aldoori WH, et al. Gut 1995; 36:276-282)
PHYSICAL ACTIVITY(Total MET)
DIETARY FIBRE INTAKE (g/d)
0.851.21
1.0
1.811.43
0.80
2.56
1.551.20
Rel
ativ
e R
isk
• There is evidence that regular and consistent use of NSAIDs and acetaminophen is associated with complicated DD
• Most of this positive association was attributable to cases associated with bleeding
THANK YOU
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