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Coffee consumption and markers of inflammation and endothelial

dysfunction in healthy and diabetic women1 3


Esther Lopez-Garcia, Rob M van Dam, Lu Qi, and Frank B Hu

KEY WORDS
Coffee, inflammation, C-reactive protein,
CRP, endothelial dysfunction, cross-sectional study, Nurses Health
Study, type 2 diabetes, women

INTRODUCTION

Increasing evidence points to inflammation and endothelial


dysfunction as common features in the group of alterations constituting the metabolic syndrome: hyperglycemia, insulin resistance, hyperinsulinemia, hypertension, obesity, and dyslipidemia (1), all of which are risk factors for cardiovascular disease.

888

Evidence also exists that dietary factors might influence the risk
of cardiovascular disease through modulation of endothelial
function (2 4).
Several studies have found that coffee consumption is associated with an impairment of the flow-mediated dilatation of the
brachial artery (5), aortic stiffness, and wave reflections (6). In
addition, a cross-sectional study found that moderate coffee consumption is related to an increase in plasma concentrations of
several markers of general inflammation (7). On the other hand,
prospective studies have reported that coffee consumption is not
associated with an increased risk of coronary heart disease (8
10), and epidemiologic studies have consistently linked coffee
consumption with a lower risk of type 2 diabetes mellitus (11). In
the present study, we evaluated the associations between longterm consumption of caffeinated and decaffeinated filtered coffee and plasma markers of inflammation and endothelial dysfunction in healthy and diabetic women in the Nurses Health
Study (NHS).
SUBJECTS AND METHODS

Subjects
The NHS was established in 1976 and included 121 700 female registered nurses residing in the United States. Every 2 y,
participants are mailed a follow-up questionnaire to update information about their medical history, lifestyle, and other risk
factors. The present study included 2 subcohorts. One subcohort
consisted of 730 women selected as control subjects for an earlier
nested case-control study of type 2 diabetes (12) and who had not
been diagnosed with cardiovascular disease, cancer, or type 2
diabetes mellitus at the time of the blood collection in 1989
1990. The second subcohort included 663 women who provided
blood samples and had a confirmed diagnosis of type 2 diabetes
mellitus but not of cardiovascular disease or cancer (13). We also
excluded those women who reported insulin use, because this
1
From the Departments of Nutrition (EL-G, RMvD, LQ, and FBH) and
Epidemiology (FBH), Harvard School of Public Health and the Channing
Laboratory (FBH), Harvard Medical School, Boston, MA.
2
Supported by NIH research grants HL65582 and DK58845. FBH was
partially supported by an American Heart Association Established Investigator Award.
3
Reprints not available Address correspondence to E Lopez-Garcia, Department of Preventive Medicine, Universidad Autonoma de Madrid, Arzobispo Morcillo, 2 Madrid, Spain. E-mail: esther.lopez@uam.es.
Received February 9, 2006.
Accepted for publication May 18, 2006.

Am J Clin Nutr 2006;84:888 93. Printed in USA. 2006 American Society for Nutrition

Downloaded from www.ajcn.org by on November 6, 2009

ABSTRACT
Background: In several short-term studies, coffee consumption has
been associated with impairment of endothelial function.
Objective: The objective was to assess the relation between longterm caffeinated and decaffeinated filtered coffee consumption and
markers of inflammation and endothelial dysfunction.
Design: We conducted a cross-sectional study of 730 healthy
women and 663 women with type 2 diabetes from the Nurses Health
Study I cohort, who were aged 4370 y and free of cardiovascular
disease and cancer at the time blood was drawn (1989 1990). Dietary intake was assessed with a validated food-frequency questionnaire in 1986 and 1990.
Results: About 77% of the healthy women consumed 1 cup (237
mL) caffeinated coffee/mo and 75% consumed 1 cup decaffeinated coffee/mo; the corresponding intakes for women with type 2
diabetes were 74% and 63%, respectively. In healthy women, no
appreciable differences in plasma concentrations of the markers
were found across categories of caffeinated coffee intake. In women
with type 2 diabetes, higher caffeinated coffee consumption was
associated with lower plasma concentrations of E-selectin (adjusted
percentage change per 1 cup/d increment 3.2%; P 0.05) and
C-reactive protein (adjusted percentage change 10.2%; P
0.001). Higher decaffeinated coffee consumption was associated
with lower plasma concentrations of E-selectin (adjusted percentage
change 2.5%; P 0.08) and C-reactive protein (adjusted percentage change 7.9%; P 0.02) only in healthy women. The
results were similar when we also adjusted the models for other
dietary factors and blood lipids and when we excluded participants
with hypertension or hypercholesterolemia.
Conclusions: These results indicate that neither caffeinated nor
decaffeinated filtered coffee has a detrimental effect on endothelial
function. In contrast, the results suggest that coffee consumption is
inversely associated with markers of inflammation and endothelial
dysfunction.
Am J Clin Nutr 2006;84:888 93.

COFFEE AND ENDOTHELIUM

hormone has antiinflammatory properties (14). The average ages


of the women at the time of the blood collection in the 2 subcohorts were 56 and 58 y, respectively (range: 4370 y). The Harvard School of Public Health and Brigham and Womens Hospital Human Subjects Committee Review Board approved the
study protocol.
Blood collection and assessment of markers

Assessment of coffee consumption


In 1986 and 1990, a semiquantitative food-frequency questionnaire (FFQ) was mailed to the participants. The FFQ included 116 food items with specified serving sizes that were
described by using natural portions or standard weight and volume measures of the servings commonly consumed in this study
population. On each questionnaire, the participants were asked
how often on average during the previous year they had consumed caffeinated or decaffeinated coffee. The participants
could choose from 9 responses (never, 13 times/mo, 1 time/wk,
2 4 times/wk, 5 6 times/wk, 1 time/d, 23 times/d, 4 5 times/d,
and 6 times/d). The method of coffee preparation was assessed
in 1990. Using the US Department of Agriculture foodcomposition sources (16) supplemented with other sources, we
estimated the nutrient content of the foods. We assessed the total
intake of nutrients by summing the nutrient content for the specific amount of each food multiplied by a weight proportional to
the frequency of its use. These values were adjusted for total
energy intake by the residual approach (17).
In our validation study, we obtained high correlations between
consumption of coffee from the FFQ and consumption estimated
from repeated 1-wk diet records (r 0.78) (18). The mean coffee
intakes (cups/d; 1 cup 237 mL) estimated by diet records
according to categories of the FFQ were 0.24 for 1 cup/mo,
0.97 for 1 cup/d, and 1.85 for 23 cups/d (18). For the present
analyses, we used the average coffee consumption and nutrient
intakes in 1986 and 1990 to represent long-term dietary consumption and to reduce measurement error. Coffee consumption

was categorized into 4 groups: 1 cup/mo, 1 cup/mo to 4 cups/


wk, 57 cups/wk, and 2 cups/d.
Assessment of other variables
Height was assessed on the baseline questionnaire in 1976, and
body weight was assessed in 1990 (19, 20). Body mass index
(BMI) was calculated as weight (kg)/height2 (m). Physical activity in 1990 was assessed in hours per week spent on common
leisure-time physical activities expressed as metabolic equivalent hours per week (MET-h/wk) (21). Alcohol consumption was
measured as the average intake (g/d) between 1986 and 1990
(22). Hormone therapy use was ascertained among postmenopausal women, who were classified as never, past, or current
users in 1990. The concentrations of total cholesterol and triacylglycerols were measured simultaneously from the blood samples with the Hitachi 911 analyzer with reagents and calibrators
from Roche Diagnostics (Indianapolis, IN); the CV for both
measurements was 1.8%.
Statistical analysis
We used PROC GLM in SAS (23) to calculate the ageadjusted geometric means and their 95% CIs for the markers in
each category of coffee consumption. We log transformed
plasma concentrations of the markers to better approximate normal distributions. Then we calculated the exponential values of
the means and the CIs. We also calculated the means of the
markers adjusted for age (5-y categories), BMI (23.0, 23.0
24.9, 25.0 29.9, 30.0 34.9, and 35.0), quintiles of physical
activity (MET-h/wk), smoking status [never smoker, past
smoker, and current smoker (114 and 15 cigarettes/d)], alcohol consumption (nondrinker and 0 4.9, 5.0 9.9, 10 14.9,
and 15.0 g/d), current aspirin use, and postmenopausal hormone therapy (premenopausal and never, past, and current user).
Multiple linear regression analyses were used to assess the
relation between continuous coffee intake and plasma concentrations of endothelial markers. Regression coefficients were
expressed as percentage differences in dependent variables for a
specified difference in coffee consumption (1 cup/d). In addition,
we performed sensitivity analyses by further adjusting the models for nutrients and foods that had previously been associated
with endothelial function or diabetes risk (trans fatty acids, total
n3 fatty acids, cereal fiber, glycemic load, magnesium, dairy
products, processed meat, nuts, and fruit and vegetables). We
also examined whether plasma lipids (total cholesterol and triacylglycerols) might modify the associations. Finally, we repeated the analyses excluding the participants who reported high
blood pressure or hypercholesterolemia, because they could have
modified their dietary intake when the disease was diagnosed.

RESULTS

Among 730 healthy women, 77% consumed at least 1 cup of


caffeinated coffee per month and 75% women consumed at least
1 cup/mo of decaffeinated coffee. The corresponding percentages for the 663 diabetic women were 74% for caffeinated coffee
and 63% for decaffeinated coffee. There were no significant
differences among the groups.
In Table 1, we show the characteristics of both populations
stratified by the categories of total coffee consumption. Women
in the higher categories tended to smoke more cigarettes and

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Blood was collected between 1989 and 1990. Women willing


to provide blood specimens were sent instructions and a phlebotomy kit. Blood specimens were returned by overnight mail on
ice, centrifuged (1200 g, 15 min) on arrival to separate plasma
from buffy coat and red cells, and frozen in liquid nitrogen until
analyzed. Ninety-seven percent of the samples arrived within
26 h of phlebotomy. Quality-control samples were routinely
frozen along with study samples to monitor changes due to longterm storage and assay variability. All markers were measured in
the Clinical Chemistry Laboratory at Childrens Hospital in Boston. Concentrations of soluble intercellular adhesion molecule 1
(sICAM-1), E-selectin, and soluble tumor necrosis factor receptor 2 (sTNF-R2) were measured by commercial enzymelinked immunosorbent assay (R&D Systems, Minneapolis,
MN). High-sensitivity C-reactive protein (CRP) concentrations
were measured by latex-enhanced turbidimetric assay on a Hitachi 911 (Denka Seiken, Tokyo, Japan). In the subcohort of
healthy women, the interassay CVs for each biomarker were as
follows: sICAM-1, 6.110.1%; E-selectin, 6.4 6.6%; CRP,
3.4 3.8%; and sTNFR-2, 3.6 5.1%. In the diabetic subcohort,
the interassay CVs were as follows: sICAM-1, 3.3 4.8%;
E-selectin, 5.7 8.8%; CRP, 2.8 5.1%; and sTNF-R2:
2.6 4.8%. Processing times did not substantially affect the concentrations of the markers (15).

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LOPEZ-GARCIA ET AL

TABLE 1
Characteristics of the population in 1990 by categories of total coffee consumption (average between consumption in 1986 and 1990)1
Healthy women

1 cup/mo
(n 60)

1 cup/mo to
4 cups/wk
(n 80)

57 cups/
wk
(n 211)

2 cups/d
(n 379)

P for
trend

1 cup/mo
(n 71)

1 cup/mo to
4 cups/wk
(n 106)

57 cups/
wk
(n 331)

2 cups/d
(n 155)

P for
trend

56 0.92
12
26.7 0.8
14.9 2.2
8
17
23
37
4.7 1.1
84 12
285 9
2.6 0.1
0.63 0.02
5.0 0.3
105 1.9
1.2 0.2
4.6 0.4
2.1 0.2
0.11 0.02
0.31 0.04
5.6 0.4

55 0.8
4
26.1 0.6
16.8 2.3
19
28
30
40
4.3 0.9
85 9
299 9
2.4 0.1
0.68 0.01
5.0 0.3
106 2.3
1.2 0.2
2.7 0.2
1.9 0.2
0.13 0.02
0.36 0.04
6.2 0.3

57 0.5
9
26.8 0.5
14.4 1.3
25
34
27
42
4.4 0.5
171 7
298 5
2.6 0.06
0.67 0.7
4.9 0.2
104 1.1
0.6 0.05
3.4 0.1
2.0 0.1
0.13 0.01
0.34 0.02
6.2 0.2

56 0.4
16
26.1 0.3
16.3 1.8
17
30
30
46
6.8 0.6
356 10
315 3
2.5 0.04
0.70 0.01
5.0 0.1
99 0.9
0.5 0.04
3.4 0.1
2.2 0.1
0.11 0.01
0.35 0.02
5.9 0.1

0.18
0.98
0.70
0.57
0.005
0.01
0.01
0.45
0.84
0.001
0.34
0.57
0.26
0.70
0.58
0.001
0.08
0.91
0.49
0.82
0.21

57 0.8
8
32.5 0.8
13.8 2.3
45
37
20
44
1.5 0.7
83 11
284 8
1.5 0.1
0.68 0.01
5.1 0.4
107 2.3
0.9 0.1
1.3 0.2
2.0 0.2
0.23 0.06
0.31 0.08
5.2 0.6

59 0.7
3
30.8 0.5
13.8 1.6
47
41
33
41
2.8 1.2
98 12
302 8
1.5 0.06
0.67 0.02
5.2 0.3
106 1.9
0.8 0.1
0.7 0.1
2.6 0.3
0.10 0.02
0.31 0.05
4.8 0.3

59 0.4
12
30.4 0.3
12.6 0.8
45
43
22
48
2.9 0.4
211 8
309 4
1.5 0.03
0.68 0.01
5.0 0.2
103 1.0
0.5 0.04
0.9 0.1
2.9 0.2
0.11 0.01
0.33 0.03
5.2 0.2

59 0.5
24
29.5 0.5
12.2 1.2
45
37
21
45
3.7 0.6
377 22
322 6
1.6 0.05
0.67 0.01
4.9 0.2
100 1.3
0.6 0.07
0.7 0.08
3.5 0.4
0.21 0.05
0.60 0.09
7.0 0.7

0.09
0.001
0.005
0.37
0.87
0.67
0.74
0.67
0.12
0.001
0.001
0.10
0.75
0.39
0.002
0.01
0.02
0.006
0.10
0.001
0.001

MET, metabolic equivalents.


x SE (all such values).
3
-Linolenic acid eicosapentaenoic acid docosahexaenoic acid.
4
1 cup 237 mL.
2

drink more alcohol than those in the lower ones. When comparing the extreme categories, caffeine intake varied from 84 to 356
g/d among healthy women, and from 83 to 377 g/d among diabetic women; also, magnesium intake increased from 285 to 315
mg/d and from 284 to 322 mg/d, respectively. In addition, coffee
consumption was associated with lower glycemic load and lower
tea consumption.
We calculated mean plasma concentration markers by categories of coffee consumption and observed higher values for all
markers in women with type 2 diabetes (Tables 2 and 3). In
healthy women, no appreciable differences across categories of
caffeinated coffee were found, except a marginally inverse association between increasing coffee intake and decreasing
plasma concentrations of sTNF-R2 (adjusted percentage change
per 1 cup/d increment 2.1%; P 0.08 from the linear
regression model) (Table 2). In women with type 2 diabetes, we
found an inverse association of caffeinated coffee with plasma
E-selectin concentrations (adjusted percentage change 3.2;
P 0.05) and a stronger inverse association with CRP (adjusted
percentage change 10.2; P 0.001). These results were
similar when we used caffeine intake instead of caffeinated coffee consumption. For decaffeinated coffee (Table 3), we observed a marginally inverse association between coffee consumption and the concentration of E-selectin (adjusted
percentage change 2.5; P 0.08) and CRP (adjusted percentage change 7.9; P 0.02) in the subcohort of healthy
women. Finally, no association between decaffeinated coffee
and the studied markers was seen in diabetic women.
In additional analyses, we observed similar results when we
further adjusted the models for the nutrients and foods that could
confound the association. Similarly, adjustment for total cholesterol and plasma triacylglycerols did not modify the results, nor

did the exclusion of participants with a diagnosis of high blood


pressure or hypercholesterolemia.
DISCUSSION
We found no evidence for adverse effects of caffeinated or
decaffeinated coffee on markers of inflammation and endothelial
dysfunction. By contrast, we found an inverse association of
caffeinated coffee consumption with E-selectin and CRP in diabetic women and an inverse association of decaffeinated coffee
consumption with CRP in healthy women.
The role of inflammatory and endothelial dysfunction markers
in the atherogenic process has been well established. CRP is a
marker of systemic inflammation and has been shown to play a
direct role in atherosclerosis by mediating LDL uptake by macrophages, which stimulates monocyte release of inflammatory
cytokines, and also by mediating induction of monocyte chemotactic protein 1 in endothelial cells (24). The soluble TNF receptor, which is induced by TNF- and other cytokines, may attenuate the activity of TNF- but also promotes inflammation in the
absence of free TNF ligand (25). More specific markers of endothelial function are E-selectin and soluble vascular adhesion
molecule 1, which are surface and soluble leukocyte adhesion
molecules, respectively, which are overexpressed when the endothelium encounters inflammatory stimuli (26). All these molecules have been found to predict cardiovascular disease (27) and
to be associated with cardiovascular events (28, 29).
Few previous studies have examined the effect of coffee on the
endothelium. Zampelas et al (7) performed a cross-sectional
study with 3000 healthy participants from the ATTICA study, in
which coffee consumption was assessed once with a FFQ. They
found that regular coffee consumption was related to higher

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Age (y)
Current smoker (%)
BMI (kg/m2)
Physical activity (MET-h/wk)
Hypertension (%)
Hypercholesterolemia (%)
Postmenopausal hormone use (%)
Aspirin use (%)
Alcohol consumption (g/d)
Caffeine (mg/d)
Magnesium (mg/d)
trans Fat (% of energy)
Total n3 fatty acids (% of energy)3
Cereal fiber (g/d)
Glycemic load
Tea (cups/d)4
Soft drinks (servings/d)
Dairy (servings/d)
Processed meat (servings/d)
Nuts (servings/d)
Fruit and vegetables (servings/d)

Women with type 2 diabetes

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COFFEE AND ENDOTHELIUM

TABLE 2
Adjusted geometric mean (and 95% CIs) plasma concentrations of inflammation and endothelial dysfunction markers by categories of caffeinated coffee
consumption1
Caffeinated coffee consumption

1 cup/mo

57 cups/wk

2 cups/d

Percentage
differences per 1
cup/d increment

P2

167
174

121
140

189
251

253
98

252 (242, 259)


257 (247, 265)

242 (238, 255)


247 (237, 257)

245 (237, 252)


245 (237, 252)

250 (242, 257)


245 (239, 252)

0.5 (0.7, 1.7)


0.8 (2.0, 0.4)

0.40
0.22

293 (279, 308)


296 (281, 311)

302 (284, 317)


311 (293, 327)

305 (290, 317)


302 (290, 314)

299 (279, 321)


287 (268, 305)

1.1 (1.1, 3.2)


0.8 (2.9, 1.4)

0.33
0.49

44.7 (42.1, 47.9)


45.2 (42.1, 48.4)

41.7 (38.5, 45.2)


42.5 (39.3, 46.1)

43.4 (40.9, 46.5)


44.3 (41.7, 47.0)

45.2 (42.9, 47.9)


44.3 (41.7, 46.5)

1.2 (1.0, 3.4)


0.2 (1.7, 2.2)

0.28
0.85

61.6 (53.4, 66.0)


60.9 (56.8, 65.3)

58.0 (53.5, 62.8)


59.7 (55.1, 64.7)

60.3 (56.8, 64.1)


59.7 (56.8, 63.4)

55.7 (50.4, 61.6)


55.1 (50.4, 60.1)

2.5 (5.6, 0.6)


3.2 (6.2, 0.01)

0.11
0.05

0.15 (0.13, 0.18)


0.15 (0.13, 0.18)

0.16 (0.13, 0.20)


0.16 (0.13, 0.20)

0.15 (0.12, 0.18)


0.15 (0.13, 0.18)

0.14 (0.12, 0.17)


0.14 (0.12, 0.16)

2.2 (7.6, 3.5)


2.7 (7.9, 2.8)

0.45
0.33

4.76 (4.18, 5.47)


4.85 (4.31, 5.53)

3.97 (3.42, 4.62)


4.06 (3.49, 4.66)

4.01 (3.56, 4.48)


3.94 (3.56, 4.39)

3.35 (2.80, 4.01) 9.4 (14.5, 3.9)


3.29 (2.77, 3.90) 10.2 (15.2, 4.8)

2322 (2186, 2490)


2345 (2186, 2514)

2345 (2165, 2540)


2322 (2143, 2540)

2368 (2231, 2540)


2368 (2208, 2515)

2230 (2101, 2345) 1.8 (3.9, 0.4)


2230 (2122, 2368) 2.1 (4.4, 0.3)

0.09
0.08

2441 (2345, 2541)


2416 (2345, 2515)

2441 (2322, 2540)


2441 (2345, 2540)

2392 (2322, 2490)


2416 (2345, 2490)

2298 (2186, 2441) 1.3 (3.0, 0.4)


2276 (2165, 2416) 1.4 (3.1, 0.4)

0.14
0.14

0.001
0.001

sICAM-1, soluble intercellular adhesion molecule 1; CRP, C-reactive protein; sTNF-R2, soluble tumor necrosis factor receptor 2.
From multiple linear regression models for the relation between caffeinated coffee consumption (cups/d) and log-transformed markers.
3
Adjusted for age (5-y categories), BMI (in kg/m2: 23.0, 23.0 24.9, 25.0 29.9, 30.0 34.9, and 35.0), quintiles of physical activity (metabolic
equivalent hours/wk), smoking status [never smoker, past smoker, and current smoker (114 and 15 cigarettes/d)], alcohol consumption (nondrinker and
0 4.9, 5.0 9.9, 10 14.9, and 15.0 g/d), aspirin use, postmenopausal hormone therapy (premenopausal and never, past, and current user), and categories of
caffeinated soft drinks, tea, and decaffeinated coffee consumption.
1
2

plasma concentrations of interleukin 6, CRP, and TNF-. Because unfiltered coffee was included when coffee consumption
was measured, it is plausible that compounds in this beverage that
increase cholesterol concentrations also contribute to increased
inflammation and endothelial dysfunction (30). Another possible explanation for the differences between our study and theirs
is that we used data on coffee consumption from 2 different
FFQs, which reflect 4 y of consumptiona longer duration than
was used in the ATTICA study.
Our findings are somewhat consistent with the fact that coffee
consumption may reduce inflammation and markers of endothelial activation. Yukawa et al (31) conducted an in vivo study with
11 healthy males who drank 24 g coffee/d for 1 wk and found that
regular coffee ingestion reduced LDL oxidation susceptibility.
Coffee may favorably affect endothelial atherosclerotic plaques
through this pathway, because oxidized LDL is present in atherosclerotic lesions enhancing the process (32). Additionally, the
phenolic compounds of coffee (chlorogenic acid, ferulic acid,

and p-coumaric acid) have a strong protective antioxidant effect


in the endothelium. One of them, chlorogenic acid, is hydrolyzed
in the body into caffeic acid and quinic acid. In a study performed
with endothelial cells (33), a metabolite of caffeic acid, dihydrocaffeic acid, was found to increase nitric oxide synthase activity
and to scavenge intracellular reactive oxygen species.
Our study had several limitations. First, it was cross-sectional,
so we cannot infer causality from our results. Second, we cannot
exclude a certain degree of residual confounding in the analyses.
For example, it is possible that women with hypertension might
have limited their coffee consumption after the diagnosis, confounding the association. However, we performed analyses in
which those women who reported hypertension or hypercholesterolemia were excluded, and the results did not change. Third,
some degree of error is inherent in the measurement of food
consumption as well as in biochemical measures, although the
dietary questionnaire has been shown to reflect long-term intake,
and the validation data showed that coffee was among the most

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Healthy women (n)


Diabetic women (n)
sICAM-1 (g/L)
Healthy women
Age-adjusted model
Multivariable model3
Diabetic women
Age-adjusted model
Multivariable model3
E-selectin (ng/L)
Healthy women
Age-adjusted model
Multivariable model3
Diabetic women
Age-adjusted model
Multivariable model3
CRP (mg/L)
Healthy women
Age-adjusted model
Multivariable model3
Diabetic women
Age-adjusted model
Multivariable model3
sTNF-R2 (g/L)
Healthy women
Age-adjusted model
Multivariable model3
Diabetic women
Age-adjusted model
Multivariable model3

1 cup/mo to 4
cups/wk

892

LOPEZ-GARCIA ET AL

TABLE 3
Adjusted geometric mean (and 95% CIs) plasma concentrations of inflammation and endothelial dysfunction markers by categories of decaffeinated coffee
consumption1
Decaffeinated coffee consumption

1 cup/mo

57 cups/wk

2 cups/d

Percentage
differences per 1
cup/d increment

P2

256
252

200
214

162
149

112
48

248 (241, 256)


244 (237, 252)

251 (243, 260)


255 (246, 263)

247 (238, 256)


249 (240, 258)

243 (232, 255)


243 (233, 254)

0.9 (2.4, 0.7)


0.6 (2.1, 1.0)

0.26
0.47

304 (292, 317)


302 (291, 315)

296 (283, 309)


298 (286, 311)

294 (279, 310)


297 (282, 313)

308 (281, 338)


229 (273, 328)

0.3 (2.4, 3.0)


0.7 (3.3, 2.0)

0.83
0.61

46.7 (44.0, 49.1)


44.9 (42.6, 47.4)

44.8 (42.1, 47.6)


46.1 (43.5, 49.0)

40.6 (37.9, 43.4)


40.9 (38.3, 43.7)

43.0 (39.7, 46.7)


43.8 (40.4, 47.5)

3.3 (5.9, 0.5)


2.5 (5.1, 0.2)

0.06
0.08

61.8 (58.2, 65.7)


61.1 (57.6, 64.8)

58.0 (54.3, 61.9)


58.2 (54.7, 62.0)

57.6 (53.3, 62.3)


58.1 (53.8, 62.8)

59.0 (51.3, 67.7)


60.4 (52.7, 69.2)

2.0 (5.8, 2.0)


1.6 (5.4, 2.4)

0.32
0.44

0.17 (0.14, 0.19)


0.16 (0.14, 0.18)

0.15 (0.13, 0.17)


0.15 (0.13, 0.18)

0.14 (0.12, 0.17)


0.15 (0.13, 0.18)

0.13 (0.10, 0.16)


0.12 (0.10, 0.14)

7.1 (13.8, 0.2)


7.9 (14.0, 1.4)

0.06
0.02

3.95 (3.53, 4.42)


3.87 (3.49, 4.30)

4.22 (3.74, 4.77)


4.27 (3.81, 4.77)

4.00 (3.46, 4.63)


3.92 (3.41, 4.50)

4.25 (3.28, 5.50)


4.85 (3.81, 6.18)

3.5 (4.0, 11.5)


5.0 (2.2, 12.8)

0.37
0.18

2261 (2141, 2387)


2239 (2117, 2368)

2338 (2199, 2487)


2379 (2234, 2533)

2403 (2244, 2573)


2216 (2228, 2562)

2221 (2045, 2411)


2221 (2042, 2417)

0.2 (3.0, 2.6)


0.5 (3.3, 2.5)

0.89
0.76

2386 (2308, 2467)


2379 (2302, 2457)

2402 (2317, 2490)


2398 (2316, 2483)

2423 (2325, 2534)


2431 (2329, 2537)

2440 (2262, 2633)


2499 (2318, 2694)

1.2 (1.0, 3.4)


1.6 (0.6, 3.9)

0.30
0.16

sICAM-1, soluble intercellular adhesion molecule 1; CRP, C-reactive protein; sTNF-R2, soluble tumor necrosis factor receptor 2.
From multiple linear regression models for the relation between decaffeinated coffee consumption (cups/d) and log-transformed markers.
3
Adjusted for age (5-y categories), BMI (in kg/m2: 23.0, 23.0 24.9, 25.0 29.9, 30.0 34.9, and 35.0), quintiles of physical activity (metabolic
equivalent hours/wk), smoking status [never smoker, past smoker, and current smoker (114 and 15 cigarettes/d)], alcohol consumption (nondrinker and
0 4.9, 5.0 9.9, 10 14.9, and 15.0 g/d), aspirin use, postmenopausal hormone therapy (premenopausal and never, past, and current user), and categories of
caffeinated soft drinks, tea, and caffeinated coffee consumption.
1
2

accurately reported foods in the FFQ (18). In addition, the use of


repeated measurements of food consumption enabled us to
reduce within-person random error. Finally, the biomarker
measures were stable and statistically consistent for 36 h
from collection to processing (15).
In conclusion, our data did not support a detrimental effect of
coffee consumption on the endothelium. Instead, we observed
associations between higher coffee consumption and lower
plasma concentrations of several markers of inflammation
and endothelial dysfunction in both healthy and diabetic
women. These results support previous findings that filtered
coffee consumption does not increase the risk of cardiovascular disease (34).
EL-G, RMvD, LQ, and FBH conceived and designed the study, analyzed
and interpreted the data, and critically revised the manuscript for important
intellectual content. FBH acquired the data, obtained funding, supervised the

study, and provided administrative, technical, and material support. EL-G


and FBH drafted the manuscript and provided statistical expertise.
None of the authors declared a conflict of interest.

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