Consumption of coffee is associated with reduced risk of death
attributed to inflammatory and cardiovascular diseases in the Iowa
Women’s Health Study1– 4
Lene Frost Andersen, David R Jacobs Jr, Monica H Carlsen, and Rune Blomhoff
Oxidation, infection, antioxidants, mortality,
mediates the respiratory burst (5, 6). Its primary product, superoxide (O2Ҁ), can lead to other reactive oxygen species. Superoxide is also formed by the mitochondrial electron transport
chain during inflammation (5). Furthermore, induction of nitric
oxide synthases will increase the production of the · NO radical
and subsequent reactive nitrogen species (5, 6). Antioxidant
therapy (reactive oxygen species or reactive nitrogen species
decomposition catalysts or selective antioxidant enzyme
mimics) has been shown to prevent in vivo tissue injury during
inflammation (7–9).
We recently analyzed the total antioxidant capacity of several
thousand foods (10 –13) and were surprised to learn that in a
healthy Norwegian population coffee contributes 쏜60% of total
dietary antioxidants (on the basis of in vitro analysis of foods)
(13). Several different compounds contribute to coffee’s antioxidant capacity, eg, caffeine (14); polyphenols, including chlorogenic acids (15); volatile aroma compounds (16); and heterocyclic compounds, including pyrroles, oxazoles, furans, thiazoles,
thiophenes, imidazoles, and pyrazines (16, 17). Many of these are
efficiently absorbed, and plasma antioxidants increase after coffee intake (16, 18). Epidemiologic studies have found that coffee
is associated with reduced biomarkers of oxidative stress (19).
Additional interest in coffee in relation to inflammatory diseases arises because caffeic acid efficiently inhibits in mice in
vivo the activation of the transcription factor nuclear factor ␬B,
which is a central mediator of the inflammatory response (1, 20).
Recently, Schulze et al (21), in a nested case-control study of
nurses aged 30 –55 y who were followed for 24 y for incident
Inflammation is a beneficial host response to foreign challenge
or tissue injury that leads to restoration of tissue structure and
function. If prolonged, however, inflammation can contribute to
pathogenesis in diseases of infectious origin and in diseases such
as rheumatoid arthritis, gout, chronic obstructive pulmonary disease, emphysema, asthma, ischemia-reperfusion, ulcerative colitis, Crohn disease, type 1 and type 2 diabetes, several types of
neurodegenerative diseases, cancer, and atherosclerosis (1– 4).
Inflammation is closely related to oxidative stress. Many cells
produce reactive oxygen and nitrogen species during inflammation. NADPH oxidase, which is activated during inflammation,
1
From the Department of Nutrition, Institute of Basic Medical Sciences,
University of Oslo, Oslo, Norway (LFA, DRJ, MHC, and RB), and the
Division of Epidemiology and Community Health, School of Public Health,
University of Minnesota, Minneapolis, MN (DRJ).
2
The contents of this manuscript are solely the responsibilities of the
authors and do not necessarily represent the official view of the funding
bodies.
3
Supported by grants from the Norwegian Research Council, The Johan
Throne Holst Nutrition Research Foundation, and The Norwegian Cancer
Society (RB) and by a grant (RO1 CA39742) from the National Cancer
Institute (Iowa Women’s Health Study; DRJ).
4
Address reprint requests to DR Jacobs Jr, Division of Epidemiology and
Community Health, School of Public Health, University of Minnesota, 1300
South 2nd Street, Suite 300, Minneapolis, MN 55454-1015. E-mail:
jacobs@epi.umn.edu.
Received September 13, 2005.
Accepted for publication January 25, 2006.
KEY WORDS
women
INTRODUCTION
Am J Clin Nutr 2006;83:1039 – 46. Printed in USA. © 2006 American Society for Nutrition
1039
Downloaded from www.ajcn.org at UIO Bibliotak Medisin OG Helsefag/Periodika (RH) on May 10, 2006
ABSTRACT
Background: Coffee is the major source of dietary antioxidants.
The association between coffee consumption and risk of death from
diseases associated with inflammatory or oxidative stress has not
been studied.
Objective: We studied the relation of coffee drinking with total
mortality and mortality attributed to cardiovascular disease, cancer,
and other diseases with a major inflammatory component.
Design: A total of 41 836 postmenopausal women aged 55– 69 y at
baseline were followed for 15 y. After exclusions for cardiovascular
disease, cancer, diabetes, colitis, and liver cirrhosis at baseline,
27 312 participants remained, resulting in 410 235 person-years of
follow-up and 4265 deaths. The major outcome measure was
disease-specific mortality.
Results: In the fully adjusted model, similar to the relation of coffee
intake to total mortality, the hazard ratio of death attributed to cardiovascular disease was 0.76 (95% CI: 0.64, 0.91) for consumption
of 1–3 cups/d, 0.81 (95% CI: 0.66, 0.99) for 4 –5 cups/d, and 0.87
(95% CI: 0.69, 1.09) for 욷6 cups/d. The hazard ratio for death from
other inflammatory diseases was 0.72 (95% CI: 0.55, 0.93) for consumption of 1–3 cups/d, 0.67 (95% CI: 0.50, 0.90) for 4 –5 cups/d,
and 0.68 (95% CI: 0.49, 0.94) for 욷6 cups/d.
Conclusions: Consumption of coffee, a major source of dietary
antioxidants, may inhibit inflammation and thereby reduce the risk
of cardiovascular and other inflammatory diseases in postmenopausal women.
Am J Clin Nutr 2006;83:1039 – 46.
1040
ANDERSEN ET AL
diabetes, observed that coffee intake was inversely associated
with inflammatory cytokines. Similarly, Honjo et al (22) showed
that biomarkers of liver inflammation were inversely associated
with coffee consumption in 7313 Japanese men aged 48 –59 y.
Fleming et al (23) found that serum ferritin was inversely associated with coffee intake among 634 men and women aged 67–93
y. In contrast, Zampelas et al (24) reported higher concentrations
of inflammatory markers among coffee drinkers in 3042 Greek
men and women with a much wider age range of 18 – 89 y. In
the present report, we studied the association of coffee with
total and cause-specific mortality in postmenopausal women
in Iowa who answered a dietary questionnaire in 1986 and
were followed for 15 y.
The Iowa Women’s Health Study cohort comprises 41 836
women aged 55– 69 y who were recruited through a baseline
questionnaire mailed in 1986 and were followed up through
December 31, 2001. A previous report explained how selfreported baseline risk factors were assessed and defined (25).
Baseline histories of physician-diagnosed cancer (other than skin
cancer), heart disease, and angina were obtained. In the present
study, we excluded women who were not postmenopausal (n ҃
569) and those with self-reported baseline heart disease (n ҃
3459), nonskin cancer (n ҃ 3497), diabetes (n ҃ 2386), chronic
colitis (n ҃ 2357), or liver cirrhosis (n ҃ 313), as well as those
who reported 쏝600 or 쏜5000 kcal/d or left 쏜30 items blank on
the diet questionnaire (n ҃ 3096). Some exclusions overlapped;
the final sample included 28 246 women. Data were missing for
waist-hip ratio for 94 women, estrogen use for 100, physical
activity status for 405, and smoking status for 380, with some
overlap; therefore, the models referred to below contain 27 312
women. The study was reviewed and approved by the Institutional Review Board of the University of Minnesota.
Dietary intake at baseline was assessed by using a 127-item
food-frequency questionnaire (26). The participants were asked
how often on average during the previous year they had consumed a cup of coffee; the questionnaire included one question
for regular coffee and one for decaffeinated coffee. The frequency responses were as follows: never, 1–3 cups/mo, 1 cup/
wk, 2– 4 cups/wk, 5– 6 cups/wk, 1 cup/d, 2–3 cups/d, 4 –5 cups/d,
and 욷6 cups/d. Coffee is quite reliably reported; as reported
elsewhere, the 3-mo test-retest r for caffeine was 0.95, and the
correlation of caffeine intake as reported on the food-frequency
questionnaire with that in the average of five 24-h dietary recalls
was 0.82 (27).
Most deaths were identified by annual linkage of cohort identifiers to Iowa statewide death records. To find additional deaths,
identifiers of nonrespondents to the follow-up surveys were sent
to the National Death Index. Cause of death was that assigned as
the single underlying cause by state health departments as follows: cardiovascular disease [(CVD) International Classification of Diseases, Ninth Revision (ICD-9) codes 390 – 459; International Classification of Diseases, Tenth Revision (ICD-10)
codes I00-I99] and cancer (ICD-9 codes 140 –239; ICD-10 codes
C00-D48) (28) or all other codes. The other codes were further
split a priori into diseases in which inflammation plays a major
role and all remaining diseases. We categorized all infectious
diseases as inflammatory diseases (specifically in these women,
170 cases: ICD-9 classifications 11.6, 28.9, 31, 38, 38.1, 38.4,
RESULTS
The mean (앐SD) consumption of coffee in the Iowa Women’s
Health Study cohort was 2.7 앐 2.0 cups/d (237 mL per cup), of
which 1.7 앐 1.9 and 1.0 앐 1.5 cups/d were regular and decaffeinated coffee, respectively. Higher coffee consumption was
strongly associated with cigarette smoking and greater alcohol
intake (Table 1). Weaker inverse associations were seen with
Downloaded from www.ajcn.org at UIO Bibliotak Medisin OG Helsefag/Periodika (RH) on May 10, 2006
SUBJECTS AND METHODS
38.9, 42.9, 46.1, 54.3, 54.7, 70.3, 70.5, 75, 78.5, 117.5, 117.9,
137, 322.9, 323.9, 473.9, 480.9, 481, 482, 482.1, 482.3, 482.4,
482.8, 485, 486, 487.1, 540, 555.9, 566, 567.2, 614.4, and 682.6
and ICD-10 classifications A04.4, A04.7, A31.9, A41.9, A49.0,
A81.0, B18.2, B44.1, B49, B94.8, G03.9, J11.0, J11.1, J15.2,
J15.9, J18.0, J18.1, J18.9, J22, K65.9, L02.9, and N39.0). Additional categories that were defined as inflammatory diseases
were chronic neurodegenerative diseases (105 cases: ICD-9
codes 331, 332, 340, 341.9, 348.3, 355.9, and 357 and ICD-10
codes G20, G30.1, G30.9, G31.9, and G35), type 1 and type 2
diabetes (35 cases: ICD-9 codes 250, 250.1, 250.3, and 250.6 and
ICD-10 codes E10.2, E10.7, E10.9, E11.2, E11.5, E11.9, E14.4,
E14.5, E14.7, and E14.9), chronic lower respiratory diseases
(265 cases: ICD-9 codes 491.2, 491.8, 491.9, 492, 493.1, 493.9,
494, and 496 and ICD-10 codes J40, J42, J43.9, J44.0, J44.1,
J44.8, J44.9, J45.9, J46, and J47), chronic liver disease and cirrhosis (23 cases: ICD-9 codes 571.1– 6 and 573.3 and ICD-10
codes K73.2 and K74.6), chronic renal failure (12 cases: ICD-9
codes 585 and 586 and ICD-10 codes N12, N18.0, N18.9, and
N19), rheumatic diseases (32 cases: ICD-9 codes 710, 710.1,
710.4, 714, 715.3, and 725 and ICD-10 codes M05.1, M06.9,
M19.9, M30.1, M31.3, M34.9, and M46.2), and several other
diseases of the respiratory system (49 cases: ICD-9 codes 135,
136.3, 466, 507, 515, and 530.1 and ICD-10 codes J69.0, J80, and
J84.1), digestive system (15 cases: ICD-9 codes 541, 556, 558,
562.1, and 574.1 and ICD-10 codes K50.9, K52.9, K81.9, and
K85), and some others (7 cases: ICD-9 codes 279.3, 303, and 707
and ICD-10 codes E85.3, E85.4, E85.9, L40.5, and N32.1).
Statistical analyses were performed with SAS software, version 8.2 (SAS Institute, Inc, Cary, NC). Coffee consumption was
categorized into 5 groups: 0, 쏝1, 1–3, 4 –5, and 욷6 cups/d. An F
test with 4 and 27 307 degrees of freedom was used for testing
baseline differences among the coffee intake categories. Cox
proportional hazards regression analysis was used to assess the
association between coffee consumption and death, presented as
estimates of hazard ratios (HRs) and their 95% CIs. Two models
are presented, a minimally adjusted model that included adjustment only for age, smoking (5 categories: no, current smokers of
쏝15 cigarettes/wk, current smokers of 쏜15 cigarettes/wk, past
smokers of 쏝15 cigarettes/wk, past smokers of 쏜15 cigarettes/
wk), and intake of alcohol (continuous, g/d, as a quadratic function), and a fully adjusted model that included the following other
possible confounders: body mass index, waist-hip ratio, education (lower than high school, high school, higher than high
school), physical activity (low, moderate, pr high), use of estrogen (never used, current use, or past use), use of multivitamin
supplements (yes, no, or don’t know), energy intake (continuous,
kcal), and intakes of whole grain (continuous, servings/d), refined grain (continuous, servings/d), red meat (continuous, servings/d), fish and seafood (continuous, servings/d), and total fruit
and vegetables (continuous, servings/d). We performed a test for
trend by treating coffee intake as a continuous variable.
1041
COFFEE AND INFLAMMATORY AND CARDIOVASCULAR DEATH
TABLE 1
Baseline characteristics according to total coffee consumption of 27 312 women in the Iowa Women’s Health Study who were free at baseline of cancer
(other than skin), heart disease, diabetes, colitis, and liver cirrhosis, 1986
Coffee consumption (cups/d)
쏝1
1–3
4 –5
욷6
P1
2717
61.4 앐 4.22
27.4 앐 5.4
0.84 앐 0.09
2911
61.9 앐 4.2
27.0 앐 5.2
0.84 앐 0.08
13600
61.7 앐 4.2
26.7 앐 4.7
0.83 앐 0.08
5323
60.9 앐 4.1
26.4 앐 4.7
0.83 앐 0.09
2761
60.4 앐 4.0
26.3 앐 4.7
0.82 앐 0.08
쏝 0.0001
쏝 0.0001
쏝 0.0001
1.6 앐 5.7
1779 앐 604
11.6 앐 9.6
13.8 앐 10.8
5.8 앐 4.1
1.6 앐 2.3)
44.7 앐 23.0
34
81
5
7
2
5
26
27
43
43
13
26
52
2.3 앐 7.0
1715 앐 594
10.9 앐 8.7
12.8 앐 9.9
5.5 앐 4.1
1.8 앐 2.1
44.7 앐 22.5
37
77
8
7
3
5
28
27
40
42
13
26
52
4.0 앐 8.7
1789 앐 582
11.4 앐 8.6
14.3 앐 10.5
5.8 앐 3.8
1.7 앐 1.9
44.3 앐 21.0
33
70
10
8
4
7
29
26
42
41
12
27
49
5.2 앐 10.4
1846 앐 621
11.5 앐 9.0
15.3 앐 11.7
6.2 앐 4.0
1.6 앐 2.1
43.0 앐 21.2
30
56
10
12
7
15
27
24
42
40
10
27
48
5.5 앐 11.2
1897 앐 688
10.8 앐 9.4
16.9 앐 13.9
6.4 앐 4.4
1.6 앐 1.7
41.3 앐 22.1
29
40
9
14
7
30
23
21
43
37
9
28
48
쏝 0.0001
쏝 0.0001
쏝 0.0001
쏝 0.0001
쏝 0.0001
0.0009
쏝 0.0001
쏝 0.0001
쏝 0.0001
쏝 0.0001
쏝 0.0001
쏝 0.0001
쏝 0.0001
쏝 0.0001
쏝 0.0001
0.23
쏝 0.0001
쏝 0.0001
0.20
0.0003
1
F statistic with 4 27 307 df derived from ANOVA with each row variable as the dependent variable and the coffee categories as the independent variable.
x៮ 앐 SD (all such values).
3
Type of arthritis was not determined.
2
age, body mass index, physical activity, educational attainment,
intake of fruit and vegetables, intake of whole grains, and history
of arthritis; positive associations were seen with energy intake,
intake of refined grains, and red meat intake.
Although the unadjusted association of coffee intake with total
mortality was flat (data not shown), the unadjusted total mortality
rate across coffee consumption categories was downsloping
when stratified into 5 levels of smoking (Figure 1). The figure
may suggest a larger absolute difference in mortality according
to coffee intake in current smokers (from 앒45% for nondrinkers
of coffee to 35% in all other coffee-drinking categories) than in
nonsmokers (decreasing from 15% for nondrinkers of coffee to
12% or 13% in other coffee-drinking categories), but there was
no significant interaction (P ҃ 0.43 with 4 df and coffee as a
continuous variable and 5 categories of smoking). Consistent
with the limited sample sizes for these detailed comparisons,
most pairwise comparisons were not statistically significant.
Furthermore, the percentage reduction was more homogeneous
across smoking categories. The findings reported below were
similar when current smokers were omitted. Thus, the primary
message of Figure 1 is that an inverse relation between coffee
intake and total death was present even within smoking categories. Consequently, we used the 5-level smoking variable as a
covariate in all further analyses.
After adjustment for age, smoking, and alcohol, the hazard
ratio for total death rates showed an inverse association with total
coffee consumption. In the fully adjusted model, the hazard ratios
were 0.85 (95% CI: 0.76, 0.94) and 0.81 (95% CI: 0.72, 0.91) for
1–3 cups/d and 4 –5 cups/d, respectively, and were slightly
higher in those drinking 욷6 cups/d (Table 2). A U-shaped
FIGURE 1. Total mortality rate by coffee consumption and smoking
(adjusted for age) in the Iowa Women’s Health Study, 1986 –2001 (n ҃
27 312). E, never smokers (n ҃ 18 102); 䊐, past smokers of 쏝15 cigarettes/d
(n ҃ 2569); Œ, past smokers of 욷15 cigarettes/d (n ҃ 2528); 䉬, smokers of
쏝15 cigarettes/d (n ҃ 1245); ■, smokers of 욷15 cigarettes/d (n ҃ 2868).
Downloaded from www.ajcn.org at UIO Bibliotak Medisin OG Helsefag/Periodika (RH) on May 10, 2006
Participants (n)
Age (y)
BMI (kg/m2)
Waist-hip ratio
Dietary intake
Alcohol (g/d)
Energy (kcal/d)
Whole grain (servings/wk)
Refined grain (servings/wk)
Red meat (servings/wk)
Seafood (servings/wk)
Total fruit and vegetable (servings/wk)
User of multivitamin supplement (%)
Never smoker (%)
Past smoker, 쏝15 cigarettes/wk (%)
Past smoker, 욷15 cigarettes/wk (%)
Current smoker, 쏝15 cigarettes/wk (%)
Current smoker, 욷15 cigarettes/wk (%)
Moderate activity (%)
High activity (%)
Participant with high school education (%)
Participant with education higher than high school (%)
Current estrogen user (%)
Past estrogen use (%)
Problem with arthritis at baseline (%)3
0
1042
ANDERSEN ET AL
TABLE 2
Hazard ratios for total and cause-specific mortality in the Iowa Women’s Health Study according to total coffee consumption, 1986 –20011
Coffee consumption (cups/d)
쏝1
1–3
4 –5
욷6
P for
trend
436
40 836
1
1
453
43 635
0.90 (0.79, 1.03)
0.91 (0.80, 1.04)
2039
204 806
0.84 (0.75, 0.93)
0.85 (0.76, 0.94)
817
80 170
0.80 (0.71, 0.90)
0.81 (0.72, 0.91)
520
40 788
0.87 (0.76, 0.99)
0.87 (0.76, 1.00)
쏝 0.0001
0.0003
160
40 836
1
1
157
43 635
0.84 (0.67, 1.05)
0.85 (0.68, 1.06)
654
204 806
0.74 (0.62, 0.88
0.76 (0.64, 0.91)
272
80 170
0.76 (0.63, 0.93)
0.81 (0.66, 0.99)
168
40 788
0.82 (0.66, 1.03)
0.87 (0.69, 1.09)
0.03
0.144
167
40 836
1
1
152
43 635
0.81 (0.65, 1.01)
0.81 (0.65, 1.01)
868
204 806
0.95 (0.80, 1.12)
0.95 (0.81, 1.13)
329
80 170
0.83 (0.69, 1.00)
0.84 (0.70, 1.02)
217
40 788
0.93 (0.75, 1.15)
0.94 (0.76, 1.16)
0.09
0.12
109
40 836
1
1
144
43 635
1.12 (0.87, 1.43)
1.12 (0.87, 1.43)
517
204 806
0.81 (0.66, 1.00)
0.80 (0.65, 0.99)
216
80 170
0.80 (0.63, 1.01)
0.76 (0.60, 0.97)
135
40 788
0.85 (0.66, 1.10)
0.79 (0.61, 1.03)
0.004
0.0006
n ҃ 27 312. CVD, cardiovascular disease.
Adjusted for age, smoking, and intake of alcohol (alcohol, alcohol2).
3
Additionally adjusted for BMI, waist-hip ratio, education, physical activity, use of estrogens, use of multivitamin supplements, energy intake, and intakes
of whole and refined grain, red meat, fish and seafood, and total fruit and vegetables.
4
P for quadratic trend ҃ 0.005.
1
2
association was found between coffee intake and death from
CVD (P for quadratic trend ҃ 0.005) in which the hazard ratios
were 0.76 (95% CI: 0.64, 0.91) and 0.81 (95% CI: 0.66, 0.99) for
1–3 and 4 –5 cups/d, respectively, compared with 0.87 (95% CI:
0.69, 1.09) for 욷6 cups/d. Death from cancer showed no significant relation with intake of coffee per day. Death from causes
other than CVD and cancer showed a decrease in risk with increasing coffee intake. In the fully adjusted model, the hazard
ratios were 0.80 (95% CI: 0.65, 0.99) and 0.76 (95% CI: 0.60,
0.97) for 1–3 and 4 –5 cups/d, respectively, compared with 0.79
(95% CI: 0.60, 0.97) for 욷6 cups/d.
To explore the relation between non-CVD and noncancer
deaths and coffee intake further, we subdivided this group a priori
into death caused by inflammatory diseases and death caused by
injury and other causes. After adjustment for age, smoking, and
alcohol, an inverse association was observed between coffee
consumption and the 713 deaths from inflammatory disease
(Table 3). Further adjustments did not significantly influence the
hazard ratios. In the fully adjusted model, the hazard ratios for
daily consumption of 1–3, 4 –5, and 욷6 cups/d were 0.72 (95%
CI: 0.55, 0.93), 0.67 (95% CI: 0.50, 0.90), and 0.68 (95% CI:
0.49, 0.94), respectively. Excluding the first 2 y of death did not
substantially alter the findings. No significant associations were
observed between coffee intake and death caused by injury or
other causes.
Infectious diseases, a major subgroup of the inflammatory
diseases, are most often characterized by a more acute pathogenesis than the other inflammatory diseases. As shown in Table 3,
we did not observe any significant association between coffee
intake and the 170 deaths attributed to infectious diseases,
whereas the inverse relation with the 543 deaths attributed to
noninfectious inflammatory diseases was significant.
We did the same type of analysis for regular and decaffeinated
coffee and for other common beverages (Table 4). We observed
similar effects for the 2 subcategories of coffee as reported above
for total coffee intake. The coffee associations were not repeated
for other beverages, including tea, fruit juice, sugar-sweetened
drinks, diet soda, and skim, low-fat, and whole milk. Total and
CVD mortality were higher in those who reported consuming
more than one sugar-sweetened beverage per day than in those
who reported any other consumption level. Correspondingly,
there was a significant upward trend in CVD mortality with a
significant increase in those reporting 쏜2.5 drinks/d. Non-CVD
and noncancer inflammatory death risk was lower in each category of those who reported drinking skim or low-fat milk than in
nondrinkers, but the association was not graded and the trend was
not significant. Further adjustment for diet soda and skim or
low-fat milk did not substantially alter the findings described in
Tables 2 and 3.
DISCUSSION
We prospectively studied the relation of coffee drinking with
total and cause-specific mortality, with particular interest in
deaths attributed to inflammatory diseases in a cohort study of
postmenopausal women. Similar to total death, death rates from
CVD showed a U-shaped association with coffee intake, whereas
death attributed to inflammatory diseases other than CVD and
cancer decreased significantly and consistently across categories
of increasing coffee consumption. In the final fully adjusted
Downloaded from www.ajcn.org at UIO Bibliotak Medisin OG Helsefag/Periodika (RH) on May 10, 2006
Total death
No. of cases
Person-years
Minimal adjustment2
Multivariate adjustment3
CVD death
No. of cases
Person-years
Minimal adjustment
Multivariate adjustment
Death from total cancer
No. of cases
Person-years
Minimal adjustment
Multivariate adjustment
Death from diseases other than cancer and CVD
No. of cases
Person-years
Minimal adjustment
Multivariate adjustment
0
1043
COFFEE AND INFLAMMATORY AND CARDIOVASCULAR DEATH
TABLE 3
Hazard ratios for death attributed to inflammatory diseases, infectious diseases, injury, and other diseases in the Iowa Women’s Health Study according to
total coffee consumption, 1986 –20011
Coffee consumption (cups/d)
0
쏝1
1–3
욷6
P for
trend
138
80 170
0.72 (0.54, 0.97)
0.67 (0.50, 0.90)
89
40 788
0.77 (0.55, 1.05)
0.68 (0.49, 0.94)
0.004
0.0004
30
80 170
0.82 (0.44, 1.52)
0.80 (0.43, 1.49)
17
40 788
0.84 (0.41, 1.70)
0.78 (0.38, 1.59)
0.55
0.42
108
80 170
0.70 (0.50, 0.96)
0.63 (0.46, 0.88)
72
40 788
0.74 (0.52, 1.06)
0.65 (0.45, 0.94)
0.004
0.0003
30
80 170
1.96 (0.85, 4.52)
2.01 (0.87, 4.65)
14
40 788
1.75 (0.69, 4.44)
1.80 (0.71, 4.60)
0.68
0.70
48
80 170
0.70 (0.44, 1.12)
0.71 (0.44, 1.13)
32
40 788
0.85 (0.50, 1.42)
0.86 (0.51, 1.45)
0.12
0.16
n ҃ 27 312. CVD, cardiovascular disease.
Adjusted for age, smoking, and intake of alcohol (alcohol, alcohol2).
3
Additionally adjusted for BMI, waist-hip ratio, education, physical activity, use of estrogens, use of multivitamin supplements, energy intake, and intakes
of whole and refined grain, red meat, fish and seafood, and total fruit and vegetables.
1
2
model that included 27 312 women, the hazard ratio for death
from inflammatory diseases was 28% lower among coffee drinkers of 1–3 cups/d than in nondrinkers; there were further small
decreases suggestive of a threshold to 33% and 32% reductions
in the hazard ratio among those drinking 4 –5 cups and 욷6
cups/d. These trends were not seen for the consumption of other
beverages.
We did not observe any significant inverse relation between
coffee intake and death attributed to infectious diseases, whereas
the inverse association between coffee intake and noninfectious
inflammatory diseases remained strong and consistent. These
data suggest that the acute pathogenesis that often characterizes
most of the infectious diseases is less prone to the protective
effect of coffee. Individual infectious diseases may be affected
by coffee, but our data set was not large enough to justify analysis
of smaller subcategories.
We developed an a priori classification of noncardiovascular,
noncancer diseases in which inflammation plays a major role.
We acknowledge that this classification remains somewhat subjective, but the inclusion was based on the following arguments.
In addition to all infectious diseases, we included chronic degenerative diseases in which tissue degradation is causally linked to
the progression of the diseases. CVD and cancer also involve
inflammation, for example, leukocyte recruitment and expression of proinflammatory cytokines. Because they are themselves
major disease categories, we examined CVD and cancer separately from these other inflammatory diseases.
A plausible candidate mechanism for the observed inverse
association of death attributed to inflammatory diseases with
coffee may be related to recent studies indicating that coffee is the
major source of antioxidants in the diet (13, 18, 29). Chlorogenic
acid, the ester of caffeic acid with quinic acid, is the most abundant polyphenol in coffee, is readily absorbed, and has relatively
high bioavailability (15, 18).
The inverse association of coffee with death attributed to inflammatory diseases is consistent with recent findings in epidemiologic studies of an inverse association of coffee with the risk
of inflammatory diseases such as Parkinson disease (30), gallstones (31), liver cirrhosis (32), and diabetes (21). Epidemiologic
studies have also found that coffee is associated with reduced
plasma concentrations of ␥-glutamyl transpeptidase, a biomarker for oxidative stress (19), and that dietary antioxidants may
reduce the risk of inflammatory diseases (9) and diabetes (33).
Surprisingly few studies have explored the possible effect of
coffee consumption on mortality. A meta-analysis that analyzed
studies available up until 1992 of coffee use and coronary death
was nonconclusive (34). A more recent study of 11 000 men and
women aged 40 –53 y who took part in the Scottish Heart Health
Study observed that increasing coffee consumption was associated with reduced all-cause mortality (35). Similar observations
Downloaded from www.ajcn.org at UIO Bibliotak Medisin OG Helsefag/Periodika (RH) on May 10, 2006
Death attributed to inflammatory diseases
No. of cases
73
95
318
Person-years
40 836
43 635
204 806
Minimal adjustment2
1
1.09 (0.80, 1.48)
0.73 (0.57, 0.95)
Multivariate adjustment3
1
1.08 (0.80, 1.47)
0.72 (0.55, 0.93)
Death attributed to infectious diseases
No. of cases
16
17
90
Person-years
40 836
43 635
204 806
Minimal adjustment
1
0.89 (0.45, 1.75)
0.97 (0.57, 1.66)
Multivariate adjustment
1
0.90 (0.45, 1.78)
0.97 (0.57, 1.67)
Death attributed to noninfectious inflammatory diseases
No. of cases
57
78
228
Person-years
40 836
43 635
204 806
Minimal adjustment
1
1.14 (0.81, 1.61)
0.67 (0.50, 0.89)
Multivariate adjustment
1
1.13 (0.80, 1.60)
0.65 (0.48, 0.87)
Death attributed to injury
No. of cases
7
14
48
Person-years
40 836
43 635
204 806
Minimal adjustment
1
1.75 (0.71, 4.34)
1.25 (0.56, 2.77)
Multivariate adjustment
1
1.84 (0.74, 4.56)
1.27 (0.57, 2.83)
Death attributed to causes other than CVD, cancer, injury, or inflammatory disease
No. of cases
29
35
151
Person-years
40 836
43 635
204 806
Minimal adjustment
1
1.03 (0.63, 1.69)
0.90 (0.60, 1.35)
Multivariate adjustment
1
1.02 (0.62, 1.68)
0.92 (0.61, 1.37)
4 –5
1044
ANDERSEN ET AL
TABLE 4
Hazard ratios for total death and death attributed to cardiovascular and other inflammatory diseases in the Iowa Women’s Health Study according to total
intake of regular coffee, decaffeinated coffee, and other diet beverages, 1986 –20011
Category of the indicated beverage2
2
3
4
5
P for
trend
1261
116 914
1
740
74 527
0.93 (0.85, 1.01)
1354
139 530
0.88 (0.81, 0.95)
546
52 268
0.86 (0.77, 0.95)
364
26 994
0.95 (0.84, 1.07)
0.04
2073
177 603
1
785
89 071
0.83 (0.76, 0.90)
1062
109 116
0.91 (0.84, 0.98)
235
25 598
0.81 (0.71, 0.93)
110
8846
0.94 (0.78, 1.14)
0.05
1942
175 008
1
649
69 457
0.88 (0.81, 0.96)
798
83 829
0.94 (0.86, 1.02)
876
81 940
1.03 (0.95, 1.12)
1003
86 757
1
706
71 365
0.93 (0.85, 1.03)
822
81 524
0.95 (0.86, 1.04)
963
97 960
0.91 (0.83, 1.00)
771
72 627
1.00 (0.91, 1.12)
0.70
1835
174 080
1
795
77 182
1.01 (0.93, 1.10)
722
75 766
0.97 (0.89, 1.06)
729
69 802
1.00 (0.92, 1.10)
184
13 404
1.23 (1.05, 1.45)
0.03
2636
225 469
1
925
101 523
0.92 (0.85, 0.99)
543
65 455
0.86 (0.78, 0.94)
119
14 390
0.88 (0.73, 1.06)
42
3396
1.16 (0.86, 1.58)
0.43
1216
99 539
1
419
41 283
0.92 (0.82, 1.03)
740
75 024
0.93 (0.85, 1.02)
927
96 529
0.90 (0.82, 0.98)
963
97 859
0.94 (0.86, 1.02)
0.61
3254
327 188
1
418
37 446
1.05 (0.94, 1.16)
593
45 600
1.08 (0.99, 1.18)
427
1
268
0.99 (0.85, 1.16)
424
0.84 (0.74, 0.97)
184
0.93 (0.78, 1.12)
108
0.92 (0.74, 1.14)
0.10
668
1
259
0.84 (0.73, 0.97)
359
0.94 (0.82, 1.07)
90
0.99 (0.79, 1.24)
35
0.99 (0.70, 1.39)
0.88
643
1
220
0.89 (0.76, 1.04)
267
0.93 (0.81, 1.08)
281
0.99 (0.86, 1.14)
343
1
222
0.86 (0.72, 1.02)
286
0.95 (0.81, 1.11)
318
0.86 (0.74, 1.01)
242
0.90 (0.75, 1.07)
1.00
596
1
281
1.09 (0.94, 1.26)
243
1.02 (0.87, 1.19)
231
1.01 (0.86, 1.19)
60
1.34 (1.01, 1.78)
0.10
845
1
315
0.97 (0.85, 1.11)
184
0.94 (0.80, 1.10)
48
1.21 (0.90, 1.63)
19
1.78 (1.13, 2.82)
0.01
394
1
142
0.95 (0.78, 1.15)
240
0.91 (0.78, 1.07)
308
0.91 (0.78, 1.06)
327
0.98 (0.84, 1.14)
0.87
1093
1
141
1.06 (0.88, 1.27)
177
0.98 (0.83, 1.16)
0.47
0.10
0.99
0.58
(Continued)
Downloaded from www.ajcn.org at UIO Bibliotak Medisin OG Helsefag/Periodika (RH) on May 10, 2006
Total mortality
Regular coffee
No. of cases
Person-years
Multivariate-adjusted hazard ratio3
Decaffeinated coffee
No. of cases
Person-years
Multivariate-adjusted hazard ratio
Tea
No. of cases
Person-years
Multivariate-adjusted hazard ratio
Fruit juice
No. of cases
Person-years
Multivariate-adjusted hazard ratio
Sugar-sweetened drinks
No. of cases
Person-years
Multivariate-adjusted hazard ratio
Diet beverages
No. of cases
Person-years
Multivariate-adjusted hazard ratio
Skim and low-fat milk
No. of cases
Person-years
Multivariate-adjusted hazard ratio
Whole milk
No. of cases
Person-years
Multivariate-adjusted hazard ratio
Cardiovascular disease death
Regular coffee
No. of cases
Multivariate-adjusted hazard ratio3
Decaffeinated coffee
No. of cases
Multivariate-adjusted hazard ratio
Tea
No. of cases
Multivariate-adjusted hazard ratio
Fruit juice
No. of cases
Multivariate-adjusted hazard ratio
Sugar-sweetened drinkgs
No. of cases
Multivariate-adjusted hazard ratio
Diet beverages
No. of cases
Multivariate-adjusted hazard ratio
Skim milk
No. of cases
Multivariate-adjusted hazard ratio
Whole milk
No. of cases
Multivariate-adjusted hazard ratio
1
1045
COFFEE AND INFLAMMATORY AND CARDIOVASCULAR DEATH
TABLE 4 (Continued)
Category of the indicated beverage2
2
3
4
5
P for
trend
218
1
115
0.84 (0.67, 1.05)
225
0.81 (0.67, 0.97)
90
0.70 (0.55, 0.91)
65
0.79 (0.59, 1.06)
0.03
366
1
139
0.86 (0.71, 1.05)
147
0.75 (0.61, 0.91)
40
0.77 (0.56, 1.07)
21
0.93 (0.60, 1.45)
0.08
336
1
111
0.90 (0.73, 1.12)
118
0.84 (0.68, 1.04)
148
1.01 (0.83, 1.23)
160
1
120
1.06 (0.83, 1.34)
149
1.15 (0.91, 1.44)
148
0.92 (0.73, 1.16)
136
1.19 (0.92, 1.53)
0.47
307
1
134
1.00 (0.82, 1.23)
116
0.92 (0.73, 1.14)
124
0.98 (0.78, 1.22)
32
1.11 (0.75, 1.64)
0.77
477
1
125
0.77 (0.63, 0.94)
88
0.86 (0.68, 1.09)
14
0.65 (0.38, 1.11)
9
1.34 (0.69, 2.60)
0.91
237
1
60
0.73 (0.55, 0.97)
125
0.88 (0.71, 1.10)
145
0.77 (0.62, 0.97)
146
0.78 (0.63, 0.97)
0.13
527
1
77
1.12 (0.88, 1.42)
109
1.05 (0.85, 1.30)
0.89
0.28
n ҃ 27 312.
Beverage intake categories were defined as follows: Coffee: 0, 쏝1, 1–3, 4 –5, and 욷6 cups/d. Tea: 0, 쏝1, 1–3, and 쏜3 cups/d. Juice: 0 – 0.5, 1–2.5, 3–5.5,
6 –7.5, and 욷8 servings/wk. Sugar-sweetened beverages: 0, 0.5, 1–1.5, 2–7, and 욷7.5 servings/wk. Diet beverages: 0, 0.5–2, 2.5–7, 7.5–17.5, and 욷18.0
servings/wk. Skim and low-fat milk: 0, 0.5–1, 3–5.5, 7, and 욷17.5 servings/wk. Whole milk: 0, 0.5–1, and 욷3 servings/wk.
3
Adjusted for age, smoking, intake of alcohol (alcohol, alcohol2), BMI, waist-hip ratio, education, physical activity, use of estrogens, use of multivitamin
supplements, energy intake, and intakes of whole and refined grain, red meat, fish and seafood, and total fruit and vegetables.
1
2
were obtained in a recent Finnish study consisting of 20 179 men
and women aged 30 –59 y (36). In that study, the association of
coffee drinking with all-cause mortality was U-shaped, with mortality being highest among those who did not drink coffee at all.
A study by Jazbec et al (37) examined the association of coffee
consumption with all-cause mortality in Croatia. Analyses were
based on data obtained from participants recruited in 1969 with
follow-ups in 1972 (1571 men and 1793 women) and 1982 (1093
men and 1330 women). During the observation period until
1999, 568 men and 382 women died. Jazbec et al observed that
men and women who regularly drank 1–2 cups of coffee daily
had a significantly lower risk of all-cause death than did those
who did not drink coffee. No significant effects were observed
for those drinking 쏜2 cups/d. In a study from Norway, Tverdal
and Skurtveit (32) examined mortality due to liver cirrhosis at
follow-up of 51 306 men and women who underwent screening
for CVD from 1977 to 1983. After 17 y, the total number of
deaths from liver cirrhosis was 53. Death from liver cirrhosis,
adjusted for sex, age, and alcohol use, was inversely associated
with coffee consumption.
Caution is needed in generalizing our results and the results of
other cited studies because the method of preparation and the
source and type of coffee beans can vary considerably and a
variety of noncoffee foods are added to coffee in different
amounts. The method of coffee preparation has also changed
with time and varies geographically (11). In the Iowa Women’s
Health Study population, the percolator method and the filter
method are likely to have been the main coffee preparation methods, with an increasing use of the filter method over time. This
probably led to less exposure to atherogenic coffee lipids (38)
during later parts of the study period than during early study
periods. The U-shaped association between coffee intake and
CVD may also be related to how the coffee is prepared: at higher
intakes of coffee prepared by the percolator method, the intake of
atherogenic coffee lipids may outweigh the potentially beneficial
compounds in coffee. Reverse causality remains a possibility,
because there are inflammatory conditions such as rheumatoid
arthritis about which we did not ask at baseline. However, we did
exclude women with many of the most prevalent inflammatory
conditions. Residual confounding remains a possibility, particularly for smoking, alcohol, and coffee intake at the highest
levels of each. Loss to follow-up, however, was minimal. Mortality follow-up was close to complete given the use of both the
Iowa state records and the National Death Index.
In conclusion, our results are consistent with a protective effect of intake of 1–3 cups of coffee per day on total death and
death from cardiovascular and other inflammatory diseases in a
group of postmenopausal women. If our observation is reproduced in other studies and proves to be causal, the implications
Downloaded from www.ajcn.org at UIO Bibliotak Medisin OG Helsefag/Periodika (RH) on May 10, 2006
Noncardiovascular and noncancer
inflammatory death
Regular coffee
No. of cases
Multivariate-adjusted hazard ratio3
Decaffeinated coffee
No. of cases
Multivariate-adjusted hazard ratio
Tea
No. of cases
Multivariate-adjusted hazard ratio
Fruit juice
No. of cases
Multivariate-adjusted hazard ratio
Sugar-sweetened drinkgs
No. of cases
Multivariate-adjusted hazard ratio
Diet beverages
No. of cases
Multivariate-adjusted hazard ratio
Skim and low-fat milk
No. of cases
Multivariate-adjusted hazard ratio
Whole milk
No. of cases
Multivariate-adjusted hazard ratio
1
1046
ANDERSEN ET AL
are considerable, being that coffee is the second most widely
consumed drink worldwide.
LFA and DRJ had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. DRJ
and RB were responsible for the study concept and design. MHC, LFA, and
DRJ were responsible for data acquisition and analysis and interpretation of
data. RB was responsible for drafting the manuscript. LFA, DRJ, MHC, and
RB contributed to critical revision of the manuscript for important intellectual content. LFA and DRJ performed the statistical analysis. DRJ and RB
obtained funding and supervised the study. None of the authors had personal
or financial conflicts of interest.
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