the Nurses' Health Study, a longitudinal cohort study of. 121,701 women. ..... Schreiber GB, Robins M, Maffeo CE, Master
ARTHRITIS & RHEUMATISM Vol. 48, No. 11, November 2003, pp 3055–3060 DOI 10.1002/art.11306 © 2003, American College of Rheumatology
Coffee Consumption and Risk of Rheumatoid Arthritis Elizabeth W. Karlson, Lisa A. Mandl, Gideon N. Aweh, and Francine Grodstein Objective. Recent reports have suggested an association between consumption of coffee or decaffeinated coffee and the risk of rheumatoid arthritis (RA), although data are sparse and somewhat inconsistent. Furthermore, existing studies measured dietary exposures and potential confounders only at baseline and did not consider possible changes in diet or lifestyle over the followup period. We studied whether coffee, decaffeinated coffee, total coffee, tea, or overall caffeine consumption was associated with the risk of RA, using the Nurses’ Health Study, a longitudinal cohort study of 121,701 women. Methods. Information on beverage consumption was assessed with a food frequency questionnaire (FFQ) that was completed every 4 years, from baseline in 1980 through 1998. Among the 83,124 women who completed the FFQ at baseline, the diagnosis of incident RA (between 1980 and 2000) was confirmed in 480 women by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria. Relationships between intake of various beverages and the risk of RA were assessed in age-adjusted models and in multivariate Cox proportional hazards models including the cumulative average intake of each beverage during the followup period, adjusted for numerous potential confounders. In addition, for direct comparisons with prior reports, multivariate analyses were repeated using only baseline beverage information. Results. We did not find a significant association between decaffeinated coffee consumption of >4 cups/
day (compared with no decaffeinated coffee consumption) and subsequent risk of incident RA, in either an adjusted multivariate model (relative risk [RR] 1.1, 95% confidence interval [95% CI] 0.5–2.2) or a multivariate model using only baseline reports of decaffeinated coffee consumption (RR 1.0, 95% CI 0.6–1.7). Similarly, there was no relationship between cumulative caffeinated coffee consumption and RA risk (RR 1.1, 95% CI 0.8–1.6 for >4 cups per day versus none) or between tea consumption and RA risk (RR 1.1, 95% CI 0.7–1.8 for >3 cups/day versus none). Total coffee and total caffeine consumption were also not associated with the risk of RA. Conclusion. In this large, prospective study, we find little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women. Recent reports (1–3) have suggested associations between consumption of coffee or decaffeinated coffee and the risk of rheumatoid arthritis (RA). These unexpected findings have generated substantial public health interest and concern. However, data are sparse, and findings are inconsistent across the few existing studies. One study demonstrated a significant association between coffee consumption and the risk of rheumatoid factor (RF)–positive RA (1). Two other studies showed an increased risk of RA associated with consumption of decaffeinated coffee, but no such association with caffeinated coffee intake (2,3). In the 2 latter studies, findings regarding tea consumption and the risk of RA were inconsistent (2,3). The largest of these 3 studies included only 158 cases of RA. Therefore, all estimates of relative risk (RR) are unstable. Furthermore, in the previous studies information on coffee or decaffeinated coffee consumption as well as potential confounders was collected only at baseline, leading to the possibility of misclassification. Most important, cigarette smoking is likely a strong confounder of the relationship between coffee consumption and RA, because smoking is highly associated with both risk of
Supported by NIH grants AR-42630, CA-87969, AR-36308, and K08-AR-02074-1. Dr. Karlson is the recipient of an Arthritis Foundation Investigator Award. Dr. Mandl is the recipient of an American College of Rheumatology Clinician Investigator Award. Elizabeth W. Karlson, MD, Lisa A. Mandl, MD, MPH, Gideon N. Aweh, MS, Francine Grodstein, ScD: Harvard Medical School, and Brigham and Women’s Hospital, Boston, Massachusetts. Address correspondence and reprint requests to Elizabeth W. Karlson, MD, 75 Francis Street, Boston, MA 02115. E-mail:
[email protected]. Submitted for publication March 6, 2003; accepted in revised form July 8, 2003. 3055
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RA (4–11) and coffee consumption (12). Thus, because in the existing studies information on confounders such as smoking has not been updated, there is a possibility for residual confounding and a bias away from the null hypothesis if coffee drinkers are more or less likely to quit smoking than are non–coffee drinkers. We studied the relationship between coffee or tea intake and the risk of RA in a large, prospective cohort of women, with information on beverage consumption, as well as important potential confounders such as cigarette smoking, collected on an ongoing basis for 18 years. This approach permitted use of timevarying exposure data and resulted in a more precise estimate of RRs than in previous studies. PATIENTS AND METHODS Study population. The Nurses’ Health Study (NHS) is a prospective cohort of 121,701 female nurses, ages 30–55 years in 1976, when the study began. Information is collected from the subjects via biennial questionnaires regarding diseases, lifestyle, and health practices. In 1980, food frequency questionnaires (FFQ) were added every 4 years, and ⬃75% of subjects respond to the FFQ. Overall, we have maintained ⬎90% followup of the original cohort (13). All aspects of this study were approved by the Partners HealthCare Institutional Review Board. Identification of RA. From 1976 until 1982, participants self-reported a diagnosis of RA in a write-in section of the questionnaire. Since 1982, participants have been specifically asked whether RA was diagnosed by a physician. For the purposes of this study, we contacted 12,691 women reporting RA on any of the biennial questionnaires from 1976 until 2000, to ask for permission to review their medical records and to request that they complete a connective tissue disease screening questionnaire (CSQ) (14). In total, 8,173 subjects (64%) responded to the mailings. After excluding subjects who denied the diagnosis of RA (n ⫽ 1,815), those in whom RA had been diagnosed before 1976 (n ⫽ 47), those who refused to give permission for record review (n ⫽ 603), and those with negative results on the CSQ (n ⫽ 2,454), we requested medical records from 3,254 women and obtained 2,519 records with appropriate information (77%). Two rheumatologists trained in chart abstraction independently conducted a medical record review, examining the charts for the American College of Rheumatology (formerly, the American Rheumatism Association) diagnostic criteria for RA (15). Subjects for whom 4 of the 7 diagnostic criteria were documented in the medical record were considered to have definite RA. We confirmed 731 cases of definite RA, for a case confirmation rate of 29% of the medical records reviewed and 6% of the original self-reports. This is identical to the selfreported RA case confirmation rate of 6% reported for the Iowa Women’s Health Study, another large, prospective, female cohort study (2).
Exposure information. All exposure information was self-reported on the mailed questionnaires. The 1980 FFQ asked about coffee consumption in the following manner: “Coffee, not decaffeinated (cups)” in categories of “almost never, 1–3 per month, 1 per week, 2–4 per week, 5–6 per week, 1 per day, 2–3 per day, 4–6 per day, or 6⫹ per day.” We organized responses into the following categories: none, ⱕ1 cup/day, 2–3 cups/day, and ⱖ4 cups/day. Information regarding intake of tea and other foods that contain caffeine (e.g., cola beverages and chocolate) was also ascertained in 1980. Tea intake was categorized as none, ⬍0.6 cup/day, 0.6–3.0 cups/ day, and ⬎3.0 cups/day. Caffeine intake from beverages and foods was categorized as ⬍142 mg/day, 142–326 mg/day, 327–402 mg/day, 403–700 mg/day, and ⬎700 mg/day. In 1984, the FFQ was modified to ask specifically about decaffeinated coffee, in addition to coffee and tea. This version of the FFQ was used in 1984, 1986, 1990, 1994, and 1998. Between 1984 and 1998, decaffeinated coffee intake was categorized as none, ⱕ1 cup/day, 2–3 cups/day, and ⱖ4 cups/ day. Although it is possible that the information on coffee was reported somewhat differently in 1980 compared with 1984, due to the different questions, analyses of caffeinated coffee that excluded the 1980 information had results similar to those in which the 1980 information was included (although confidence intervals [CIs] were wider with the more limited followup). Thus, there was no evidence of bias in the 1980 data. We also identified and updated information on potential confounders based on the questionnaire data. Age was categorized as ⬍50 years, 50–55 years, 56–59 years, and ⱖ60 years. Cumulative pack-years of smoking was categorized as none, 1–7 pack-years, 8–17 pack-years, 18–30 pack-years, and ⱖ31 pack-years. In alternative analyses, smoking was categorized as never, current 0–14 cigarettes/day, current ⱖ15 cigarettes/day, past 0–14 cigarettes/day, and past ⱖ15 cigarettes/day. Alcohol use (red wine, white wine, beer, liquor) was ascertained every 4 years on the FFQ and was categorized as none, ⬍5 gm/day, 5–9 gm/day, 10–14 gm/day, and ⱖ15 gm/day. Body mass index (BMI) was computed for each 2-year time interval, using the most recent weight in kilograms divided by height in meters squared, as reported in 1976 (when the cohort mean age was 42.9 ⫾ 7.2 years), and categorized as ⬍22 kg/m2 (referent group), 22–24.9 kg/m2, 25–29.9 kg/m2, 30–34.9 kg/m2, and ⱖ35 kg/m2. Age at menarche was categorized as age ⱕ10 years, 11 years, 12 years, 13 years, and ⱖ14 years, with age 12 years used as the referent group. Age at first birth was categorized as age ⬍20 years, 20–24 years, 25–29 years, and ⬎29 years, with age ⬍20 years used as the referent group. Parity, categorized as 0, 1, 2, 3, and ⱖ4 children, was assessed through 1984 (after which women in the cohort were ages 38–63 years, and childbirth was uncommon). Information on oral contraceptive use was collected from 1976 until 1982 (after which women in the cohort were ages 36–61 years, and use was rare) and was categorized as never use versus ever use. Total lifetime breastfeeding history was categorized as ⬍3 months, 3–11 months, 12–23 months, and ⱖ24 total months. Use of hormone replacement therapy was categorized as current, past, never, or premenopausal. For each of the confounders, we included a category of “missing” in the analysis. For the beverage variables, data that were unavailable at baseline were categorized as missing; during followup, however, missing variables were assigned the values
COFFEE CONSUMPTION AND RA RISK
of the preceding year (if these were available), and so on. These values were then used to obtain the cumulative average. Population for analysis. For all analyses, we excluded women who did not respond to the FFQ in 1980 (baseline for this analysis), prevalent cases of RA as of 1980, women who reported RA but in whom the diagnosis was not confirmed by medical record review, and nonresponders to the supplementary questionnaire on RA. Thus, the final group studied includes 83,124 women followed up since 1980. For analyses of caffeinated coffee, tea, and total caffeine intake, followup continued from June 1980 until May 1998, and included 480 cases of incident RA. However, because data on decaffeinated coffee intake were first collected in 1984, analyses of decaffeinated coffee as well as total coffee include followup from June 1984 through May 1998. We also analyzed a subset of RA, using 283 cases of RF-positive RA in the 1980–1998 analysis, and 205 cases of RF-positive RA in the 1984–1998 analysis of decaffeinated coffee. Statistical analysis. We used Cox proportional hazards models to study the association between RA and coffee, decaffeinated coffee, total coffee, tea, and caffeine intake, adjusting for potential confounding factors (16). In this type of analysis, data for each subject include person-time of followup (from the date of receipt of the first questionnaire to the end of the followup period), the date of diagnosis of RA as defined in the medical record, and the date of death or loss to followup (whichever came first). In addition, because women may have changed their lifestyles at the onset of RA symptoms, we also conducted an alternative analysis in which followup time was censored at the date of the first symptom of RA. Relative risks were calculated as the ratio of incidence rates in subjects with caffeine exposure and in those without such exposure. Because our hypothesis was that long-term dietary patterns would be related to the risk of RA, in our primary analyses we prospectively updated dietary variables using cumulative average dietary intake based on information from each FFQ (i.e., the updated variable in 1986 would represent the average intake from the 1980, 1984, and 1986 questionnaires) (17,18). In alternative analyses, we also updated dietary variables without this cumulative averaging, to consider the possibility that only recent beverage intake is important to the risk of RA. In addition, for comparability with analyses from studies that do not have updated dietary information, we also repeated our analyses using single baseline dietary intake (in these analyses, information on covariates was not updated either).
RESULTS Characteristics of the subjects at baseline (in 1980), according to the categories of coffee consumption, are presented in Table 1. Heavy coffee drinkers were more likely to be heavy smokers, were more likely to drink alcohol, and were slightly leaner than were non–coffee drinkers. The mean age of the NHS cohort at baseline was 46.9 years (range 34–59 years), and 97% of the women were white. Among subjects with RA, the
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Table 1. Age-adjusted characteristics of subjects at baseline, according to coffee consumption* Coffee consumption, cups/day Characteristic 2
Body mass index, mean kg/m Smoking, pack-years, % 0 1–7 8–17 18–30 ⱖ31 Data missing Alcohol consumption, gm/day, % 0 ⬍5 5–9 10–14 ⱖ15 Data missing HRT use, % Premenopausal Never Past Current Data missing Oral contraceptive use, % Never Ever Parity, % 0 1 2 3 ⱖ4
0
ⱕ1
2–3
ⱖ4
24.6
24.3
24.0
24.0
54 13 11 10 10 1
52 16 12 10 8 1
42 17 15 14 12 1
29 13 14 20 23 1
44 31 8 7 8 2
32 36 10 9 10 2
26 33 11 11 15 3
28 33 11 11 14 3
55 24 9 11 2
56 24 8 10 2
56 24 8 10 2
55 26 7 10 3
51 49
50 50
50 50
51 49
7 7 29 27 30
7 8 28 27 30
7 7 27 27 31
6 7 27 27 33
* HRT ⫽ hormone replacement therapy.
mean age at diagnosis was 53.7 years, and 77% of them were RF positive. When we examined only our baseline data, coffee consumption of ⱖ4 cups/day was associated with a modest increased risk of RA (RR 1.4, 95% CI 1.0–1.8) compared with no coffee intake (Table 2); these results are similar to those of a previous study. However, when we adjusted for smoking and other covariates in an updated multivariate model that also included coffee intake throughout the followup period, the relative risk was attenuated (RR 1.1, 95% CI 0.8–1.6), and coffee intake was no longer significantly associated with the risk of RA. In addition, when we limited these analyses to 283 RF-positive cases of incident RA (Table 3), we found similar results (in the updated model, RR 1.1, 95% CI 0.7–1.8). We also did not find a significant association between consumption of ⱖ4 cups/day of decaffeinated coffee compared with no consumption of decaffeinated coffee and subsequent risk of incident RA, either in an
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Table 2. Coffee, tea, and caffeine consumption and relative risk of RA, Nurses’ Health Study, 1980–2000*
Caffeinated coffee, cups/day 0 ⱕ1 2–3 ⱖ4 Decaffeinated coffee, cups/day 0 ⱕ1 2–3 ⱖ4 Total coffee, cups/day 0 ⱕ1 2–3 ⱖ4 Tea, cups/day 0 ⬍0.6 0.6–3.0 ⬎3.0 Caffeine, mg/day ⬍142 142–326 327–402 403–700 ⬎700 Smoking, pack-years¶ 0 1–7 8–17 18–30 ⱖ31
Updated multivariate‡
Age-adjusted
Baseline multivariate§
No. of RA cases†
Personyears
RR
95% CI
RR
95% CI
RR
95% CI
63 97 245 75
248,312 348,444 737,607 227,129
1.0 1.1 1.3 1.3
Referent 0.8–1.5 1.0–1.7 0.9–1.8
1.0 1.1 1.2 1.1
Referent 0.8–1.5 0.9–1.6 0.8–1.6
1.0 1.3 1.3 1.4
Referent 1.0–1.7 1.0–1.6 1.0–1.8
131 129 93 8
388,785 453,249 243,299 19,709
1.0 0.8 1.1 1.2
Referent 0.7–1.1 0.9–1.4 0.6–2.4
1.0 0.9 1.1 1.1
Referent 0.7–1.1 0.9–1.5 0.5–2.2
1.0 1.1 1.2 1.0
Referent 0.8–1.4 0.9–1.6 0.6–1.7
6 30 187 78
202,763 131,274 591,419 179,586
1.0 0.7 1.0 1.3
Referent 0.5–1.1 0.7–1.3 1.0–1.8
1.0 0.8 0.9 1.2
Referent 0.5–1.2 0.7–1.2 0.9–1.7
1.0 0.9 1.1 1.2
Referent 0.6–1.3 0.8–1.5 0.9–1.7
87 202 172 18
305,121 648,643 544,621 62,402
1.0 1.1 1.1 1.0
Referent 0.8–1.4 0.9–1.4 0.6–1.7
1.0 1.2 1.2 1.1
Referent 0.9–1.5 0.9–1.6 0.7–1.8
1.0 1.0 1.0 1.1
Referent 0.8–1.3 0.8–1.2 0.7–1.6
83 84 93 110 110
292,823 312,383 321,265 320,444 318,916
1.0 1.0 1.0 1.2 1.2
Referent 0.7–1.3 0.8–1.4 0.9–1.6 0.9–1.6
1.0 0.9 0.9 1.1 1.0
Referent 0.7–1.2 0.7–1.3 0.8–1.5 0.8–1.4
1.0 1.1 1.0 1.2 1.2
Referent 0.8–1.4 0.8–1.4 0.9–1.6 0.9–1.6
165 58 55 80 110
683,357 221,865 183,389 180,366 258,549
1.0 1.1 1.3 1.9 1.7
Referent 0.8–1.5 0.9–1.7 1.4–2.4 1.3–2.2
1.0 1.1 1.2 1.8 1.6
Referent 0.8–1.4 0.9–1.7 1.4–2.4 1.3–2.1
1.0 1.1 1.2 1.8 1.6
Referent 0.8–1.5 0.9–1.7 1.4–2.4 1.3–2.1
* Analyses of caffeinated coffee, tea, caffeine, and smoking included information from the 1980–1998 questionnaires (n ⫽ 480 rheumatoid arthritis [RA] cases). Analyses of decaffeinated coffee and total coffee were limited to data from the 1984–1998 questionnaires (n ⫽ 361 RA cases). RR ⫽ relative risk; 95% CI ⫽ 95% confidence interval. † Data on tea were missing for 1 subject, and data on smoking were missing for 12 subjects. ‡ Adjusted for age, alcohol use, smoking, body mass index (BMI), age at menarche, age at first birth, parity, breastfeeding, oral contraceptive use, and use of hormone replacement therapy, using updated information obtained during the followup period. § Adjusted for age, alcohol use, smoking, BMI, age at menarche, age at first birth, parity, breastfeeding, oral contraceptive use, and use of hormone replacement therapy, using only baseline data. ¶ P trend ⬍0.0001, ⱖ31 pack-years of smoking versus none.
age-adjusted model (RR 1.2, 95% CI 0.6–2.4), an updated multivariate model (RR 1.1, 95% CI 0.5–2.2), or a multivariate model that included only baseline reports of consumption of decaffeinated coffee (RR 1.0, 95% CI 0.6–1.7) (Table 2), using followup data collected since 1984. We found no evidence for a protective effect of tea on the risk of RA (updated multivariate RR 1.1, 95% CI 0.7–1.8 for ⬎3 cups/day compared with no consumption). Total coffee and total caffeine consumption were also not associated with the risk of RA. Analyses using baseline exposures and analyses of the RF-positive cases showed similar results. As expected, cigarette smoking was associated
with a significantly increased risk of developing RA; ⬎30 pack-years of smoking compared with no smoking demonstrated a multivariate RR of 1.6 (95% CI 1.3–2.1, P trend ⬍0.0001) (Table 2). This association was consistent across all types of analyses: the age-adjusted analysis, the updated multivariate analysis, and the multivariate analysis using only baseline reports of smoking in 1980. We repeated the models, substituting a smoking variable with current and past smoking exposure data, and for current smokers of ⱖ15 cigarettes/day the RR was 1.8 (95% CI 1.4–2.2), while for past smokers of ⱖ15 cigarettes/day the RR was 1.4 (95% CI 1.0–1.9) (data not shown).
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Table 3. Coffee, tea, and caffeine consumption and relative risk of RF-positive RA, Nurses’ Health Study, 1980–2000*
Caffeinated coffee, cups/day 0 ⱕ1 2–3 ⱖ4 Decaffeinated coffee, cups/day 0 ⱕ1 2–3 ⱖ4 Total coffee, cups/day‡ 0 ⱕ1 2–3 ⱖ4 Tea, cups/day 0 ⬍0.6 0.6–3.0 ⬎3.0 Caffeine, mg/day ⬍142 142–326 327–402 403–700 ⬎700
Updated multivariate†
Age-adjusted
No. of RA cases
Person-years
RR
95% CI
RR
95% CI
35 61 144 43
248,338 348,475 737,686 227,163
1.0 1.3 1.3 1.3
Referent 0.8–1.9 0.9–2.0 0.9–2.1
1.0 1.3 1.3 1.1
Referent 0.8–1.9 0.9–1.9 0.7–1.8
76 73 52 4
388,831 453,296 243,331 19,712
1.0 0.8 1.1 1.0
Referent 0.6–1.1 0.8–1.5 0.4–2.8
1.0 0.9 1.1 1.0
Referent 0.6–1.2 0.8–1.6 0.3–2.6
31 20 107 47
202,792 131,282 591,494 179,613
1.0 1.0 1.2 1.7
Referent 0.6–1.8 0.8–1.8 1.1–2.7
1.0 1.1 1.2 1.5
Referent 0.6–1.9 0.8–1.8 0.9–2.4
47 133 92 11
305,158 648,698 544,690 62,411
1.0 1.3 1.1 1.2
Referent 1.0–1.9 0.8–1.6 0.6–2.2
1.0 1.5 1.2 1.2
Referent 1.0–2.1 0.9–1.8 0.6–2.3
53 45 54 68 62
292,848 312,416 321,300 320,474 318,962
1.0 0.8 0.9 1.2 1.1
Referent 0.5–1.2 0.6–1.4 0.8–1.7 0.7–1.5
1.0 0.7 0.9 1.1 0.9
Referent 0.5–1.1 0.6–1.3 0.7–1.5 0.6–1.3
* Analyses of caffeinated coffee, tea, and caffeine included information from the 1980–1998 questionnaires (n ⫽ 283 cases of rheumatoid factor [RF]–positive rheumatoid arthritis [RA]). Analyses of decaffeinated coffee and total coffee were limited to data from the 1984–1998 questionnaires (n ⫽ 205 cases of RF-positive RA). RR ⫽ relative risk; 95% CI ⫽ 95% confidence interval. † Analysis of cumulative average intake of coffee, decaffeinated coffee, tea, and caffeine variables, adjusted for age, alcohol use, smoking, body mass index, age at menarche, age at first birth, parity, breastfeeding, oral contraceptive use, and use of hormone replacement therapy, using updated information obtained during the followup period. ‡ P trend 0.02, ⱖ4 cups/day versus none, in the age-adjusted model.
We repeated all analyses without averaging beverage intake data from all previous FFQs (i.e., we updated data at each time period using only the FFQ administered during that time period) to assess the hazard associated with recent intake, and the results were similar to those presented above. In addition, we repeated the analyses using information on beverages as well as potential confounding factors reported prior to the date of first symptom of RA, and found similar results (data not shown). DISCUSSION In contrast to previous reports, in this large prospective cohort of women, we find no association between consumption of coffee, decaffeinated coffee, tea, caffeine, or total coffee and risk of developing RA. We do find a significant association between smoking
and risk of RA, as has been shown by multiple other studies (4–11). An important distinction between the present study and previous analyses of coffee and tea is our ability to update information on both beverage intake and potential confounders; we do not assume that the initial information reported at baseline remains unchanged over time. In particular, our analyses suggest that the results of previous studies showing an increased risk of RA for coffee drinkers relative to non–coffee drinkers may be attributable to residual confounding by smoking, because smoking habits (and other factors) may differentially change over time among persons who drink coffee and those who do not. Specifically, coffee drinkers could be more likely to continue smoking, while those who do not drink coffee could be more likely to stop smoking; thus, updated information on smoking status is critical to
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properly control for smoking. Indeed, in our population, coffee drinkers were 25% less likely to quit smoking over the followup period than were non–coffee drinkers. Furthermore, the results of 3 previous studies regarding coffee exposures and the relative risk of RA are inconsistent and may be explained by chance findings. Analysis of prospective data from the Mini-Finland Health Survey of ⬃7,000 subjects, including 69 cases of RF-positive RA, with baseline data from 1973 through 1977 (with followup through 1989), demonstrated an increased risk of RF-positive RA, with an RR of 2.2 (95% CI 1.13–4.27) for those drinking ⱖ4 cups of coffee daily compared with those drinking ⬍4 cups/day, after adjusting for smoking, age, sex, serum cholesterol level, and BMI at baseline (1). However, analysis of prospective data from the Iowa Women’s Health Study on 31,000 women (including 158 cases of incident RA, with baseline data on beverage intake collected in 1986 and incident RA determined from followup questionnaires in 1992 and 1997) demonstrated an increased relative risk of RA associated with baseline consumption of ⱖ4 cups/day of decaffeinated coffee (RR 2.58, 95% CI 1.63–4.06) compared with no consumption, but no association with baseline intake of caffeinated coffee or daily caffeine intake was observed (2). In the Iowa study, women consuming ⬎3 cups of tea per day at baseline showed a decreased risk of RA (RR 0.39, 95% CI 0.16–0.97) compared with women who never drank tea. In that study, models were adjusted for age, marital status, smoking history, age at menopause, and use of hormone replacement therapy. Finally, a nested case–control study in a prospective cohort of 64,000 women in the Black Women’s Health Study (3) demonstrated an increased risk of RA for both those who drank ⱖ1 cup/day of decaffeinated coffee (OR 3.9, 95% CI 1.8–8.3) and for those who drank ⱖ1 cup of tea daily (OR 2.1, 95% CI 1.0–4.2). In that study, data were collected only at baseline. Thus, existing data offer no clear evidence of an increase in the risk of RA for coffee drinkers or tea drinkers, and our findings further support null associations. In conclusion, there is little evidence to support a consistent association between coffee, decaffeinated coffee, or tea and the relative risk of RA. ACKNOWLEDGMENTS We thank the dedicated nurses in the NHS, who have now participated in the study for more than 25 years. We also
thank Christine Jones for her efforts to obtain medical record information, and Karen Corsano for her programming assistance.
REFERENCES 1. Helio ¨vaara M, Aho K, Knekt P, Impivaara O, Reunanen A, Aromaa A. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann Rheum Dis 2000;59:631–5. 2. Mikuls TR, Cerhan JR, Criswell LA, Merlino L, Mudano AS, Burma M, et al. Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 2002;46:83–91. 3. Formica MK, Palmer JR, Rosenberg L, McAlindon TE. Lifestyle factors associated with the development of rheumatoid arthritis (RA): results for the Black Women’s Health Study (BWHS). Arthritis Rheum 2001;44 Suppl 9:S376. 4. Vessey MP, Villard-Mackintosh L, Yeates D. Oral contraceptives, cigarette smoking and other factors in relation to arthritis. Contraception 1987;35:457–64. 5. Hernandez Avila M, Liang MH, Willett WC, Stampfer MJ, Colditz GA, Rosner B, et al. Reproductive factors, smoking, and the risk for rheumatoid arthritis. Epidemiology 1990;1:285–91. 6. Helio ¨vaara M, Aho K, Aromaa A, Knekt P, Reunanen A. Smoking and risk of rheumatoid arthritis. J Rheumatol 1993;20:1830–5. 7. Voigt LF, Koepsell TD, Nelson JL, Dugowson CE, Daling JR. Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis. Epidemiology 1994;5:525–32. 8. Silman AJ, Newman J, MacGregor AJ. Cigarette smoking increases the risk of rheumatoid arthritis: results from a nationwide study of disease-discordant twins. Arthritis Rheum 1996;39:732–5. 9. Symmons DP, Bankhead CR, Harrison BJ, Brennan P, Barrett EM, Scott DG, et al. Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis: results from a primary care–based incident case–control study in Norfolk, England. Arthritis Rheum 1997;40:1955–61. 10. Karlson EW, Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Arthritis Rheum 1999;42:910–7. 11. Criswell LA, Merlino LA, Cerhan JR, Mikuls TR, Mudano AS, Burma M, et al. Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal women: results from the Iowa Women’s Health Study. Am J Med 2002;112:465–71. 12. Schreiber GB, Robins M, Maffeo CE, Masters MN, Bond AP, Morganstein D. Confounders contributing to the reported associations of coffee or caffeine with disease. Prev Med 1988;17:295–309. 13. Colditz GA, Manson JE, Hankinson SE. The Nurses’ Health Study: 20-year contribution to the understanding of health among women. J Womens Health 1997;6:49–62. 14. Karlson EW, Sanchez-Guerrero J, Wright EA, Lew RA, Daltroy LH, Kalz JN, et al. A connective tissue disease screening questionnaire for population studies. Ann Epidemiol 1995;5:297–302. 15. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24. 16. SAS/STAT user’s guide: version 6, 4th ed. Cary, NC: SAS Institute; 1990. 17. Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Rosner BA, et al. Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 1997;337:1491–9. 18. Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Speizer FE, et al. Dietary protein and risk of ischemic heart disease in women. Am J Clin Nutr 1999;70:221–7.
