ArticlePDF Available

Letter: Coffee consumption and gallstone disease - A cautionary note on the assignment of exposure values in dose-response meta-analyses

Authors:
Letters to the Editors
Letter: coffee consumption and gallstone
disease a cautionary note on the
assignment of exposure values in
doseresponse meta-analyses
A. Crippa*
,
, A. Discacciati*
,
, N. Orsini*
,
&
V. Oskarsson*
*Unit of Nutritional Epidemiology, Institute of Environmental
Medicine, Karolinska Institutet, Stockholm, Sweden.
Unit of Biostatistics, Institute of Environmental Medicine, Karolinska
Institutet, Stockholm, Sweden.
E-mail: viktor.oskarsson@ki.se
doi:10.1111/apt.13428
SIRS, We read with interest the doseresponse meta-anal-
ysis by Zhang et al., where the authors reported a non-
linear inverse association between coffee consumption
and risk of gallstone disease (P
non-linearity
<0.05).
1
This
analysis was based on four prospective cohort studies
that presented results for several categories of coffee con-
sumption.
24
According to common practice, Zhang
et al. assigned the mid-point of each category as a proxy
for the exposure level. For the highest open-ended cate-
gory, however, the mid-point was set at 1.5 times the
lower boundary, which is quite unusual and may lead to
too high values of coffee consumption (up to 9 cups/
day). In this letter, we would like to discuss the conse-
quences of that exposure assignment and, by doing so,
draw attention to the importance of sensitivity analyses
in doseresponse meta-analyses.
Data were reanalysed using different methods of expo-
sure assignment. In addition to that of Zhang et al.
(which referred to a meta-analysis on egg consumption),
we used a method proposed in two recent meta-analyses
on coffee consumption.
5, 6
This method is different
in only one respect; it assumes that the highest open-
ended category has the same amplitude as the preceding
one, which may lead to more reasonable values of coffee
consumption (up to 6.5 cups/day). For comparison, we
obtained the actual median values directly from the
authors of the original studies (up to 7 cups/day). Statis-
tical analyses were conducted with the R package dosres-
meta.
7
Compared to the median values, Zhang et al.s mid-
points overestimated the coffee consumption in the high-
est categories by at least 22%. In contrast, the alternative
mid-points were much closer to the median values
(8%). As expected, we observed a non-linear inverse
association between coffee consumption and risk of gall-
stone disease when using Zhang et al.s mid-points
(P
non-linearity
<0.05) (Figure 1). However, there was no
evidence of a nonlinear association when using the other
methods of exposure assignment, neither the alternative
mid-points (P
non-linearity
=0.60) nor the median values
(P
non-linearity
=0.69). Furthermore, using either of these
two methods, the inverse association was stronger than
that reported by Zhang et al. For example, the hazard
ratio (95% condence interval) for 6 cups/day vs. 0
cups/day was 0.66 (0.510.85) when we used the median
values [previously reported to be 0.75 (0.640.88)].
The issues we have discussed in this letter do not
change Zhang et al.s conclusion that coffee consumption
is related to a decreased risk of gallstone disease. How-
ever, they do change the interpretation of the dose
response results, that is, the shape and magnitude of the
exposure-disease association (which is highly relevant
given the widespread consumption of coffee and the high
incidence of gallstones).
More broadly, this letter exemplies the general
importance of exposure assignment in doseresponse
meta-analyses. Whenever possible, we encourage meta-
analysts to retrieve information on the exposure distribu-
tion directly from the original authors. We also recom-
mend that sensitivity analyses are routinely performed to
examine whether the assigned exposure values have a
strong inuence on the doseresponse results.
AP&T invited editorial and correspondence columns are restricted to letters discussing papers that have been published
in the journal. A letter must have a maximum of 500 words, may contain one table or gure, and should have no more
than 10 references. It should be submitted electronically to the Editors via http://mc.manuscriptcentral.com/apt.
ª2015 John Wiley & Sons Ltd166
Alimentary Pharmacology and Therapeutics
ACKNOWLEDGEMENTS
The authors thank Michael Leitzmann, Diane Feskanich and Caro-
line Nordenvall for providing original data on coffee consumption.
Declaration of personal and funding interests: None.
REFERENCES
1. Zhang YP, Li WQ, Sun YL, Zhu RT, Wang WJ. Systematic
review with meta-analysis: coffee consumption and the risk
of gallstone disease. Aliment Pharmacol Ther 2015; 42:
63748.
2. Nordenvall C, Oskarsson V, Wolk A. Inverse association
between coffee consumption and risk of cholecystectomy in
women but not in men. Clin Gastroenterol Hepatol 2015; 13:
1096102.e1.
3. Leitzmann MF, Willett WC, Rimm EB, et al. A prospective study
of coffee consumption and the risk of symptomatic gallstone
disease in men. JAMA 1999; 281: 210612.
4. Leitzmann MF, Stampfer MJ, Willett WC, Spiegelman D, Colditz
GA, Giovannucci EL. Coffee intake is associated with lower risk
of symptomatic gallstone disease in women. Gastroenterology
2002; 123: 182330.
5. Discacciati A, Orsini N, Wolk A. Coffee consumption and risk of
nonaggressive, aggressive and fatal prostate cancera dose
response meta-analysis. Ann Oncol 2014; 25: 58491.
6. Crippa A, Discacciati A, Larsson SC, Wolk A, Orsini N. Coffee
consumption and mortality from all causes, cardiovascular
disease, and cancer: a dose-response meta-analysis. Am J
Epidemiol 2014; 180: 76375.
7. Crippa A, Orsini N. Dosresmeta: performing multivariate dose-
response meta-analysis. Available at: http://CRAN.R-
project.org/package=dosresmeta (accessed 18 September 2015).
Letter: coffee consumption and gallstone
disease a cautionary note on the
assignment of exposure values in dose
response meta-analyses. Authorsreply
Y.-P. Zhang
1
, W.-Q. Li
1
, Y.-L. Sun, R.-T. Zhu & W.-J. Wang
Department of Hepatobiliary and Pancreatic Surgery, School of
Medicine, Institute of Hepatobiliary and Pancreatic Diseases, The First
Afliated Hospital of Zhengzhou University, Zhengzhou University,
Zhengzhou, China.
E-mail: ylsun@zzu.edu.cn.
doi:10.1111/apt.13442
1
These authors contributed equally to this work.
SIRS, We would like to thank Crippa and colleagues for
their letter regarding our recent article.
1, 2
They raised
the point that different exposure assignment values
might change the shape of the doseresponse curve in
meta-analyses and, thus, encouraged direct retrieval of
the exposure distribution data from the original authors.
We whole-heartedly agree with this point. However, dis-
cussion of this issue is warranted.
In assigning a single value between boundaries in each
category of exposure, the summary slope of individual
doseresponse studies might be sensitive to the method
of assignment.
3
According to Berlin et al.,
4
assigning a
mean value to each category may reduce the apparent
0.6
0.7
0.8
0.9
1.0
Coffee consumption (cups/day)
Hazard ratio
0123456789
Figure 1 | Pooled doseresponse association between coffee consumption and risk of gallstone disease when using different
exposure assignments for the highest open-ended category: assigning a mid-point of 1.5 times the lower boundary (dotted
line); assigning a mid-point under the assumption that the category had the same amplitude as the preceding one (dashed
line); and assigning the actual median value (solid line). The hazard ratios are plotted on the log scale.
Aliment Pharmacol Ther 2016; 43: 166180 167
ª2015 John Wiley & Sons Ltd
Letters to the Editors
... For the remainder classes, the mid of each quantile was assigned to the respective HR. For classes with the highest consumption, if these were openended, we assumed that the range of category was the same as the closest category and we also assigned the mid-point of the case to the estimate for the meta-analysis [16]. A potential non-linear relationship between coffee consumption and the risk of clinical events was evaluated through restricted cubic splines with three knots at 10, 50, and 90% of the distribution [17]. ...
Article
Background and Aims This systematic review aims to evaluate the impact of coffee consumption in patients with previous myocardial infarction (MI), in relation to all-cause and cardiovascular mortality, as well as other major cardiovascular events (MACE) such as stroke, heart failure, recurrent MI and sudden death. Methods and Results MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection, SciELO Citation Database, Current Contents Connect®, KCI Korean Journal Database, African Index Medicus, and LILACS were searched for longitudinal studies evaluating the impact of coffee consumption in patients with previous myocardial infarction. We performed a random-effects meta-analysis to estimate the pooled hazard ratios (HR) with 95% confidence intervals (CI). The statistical heterogeneity was measured by I². A dose-response analysis was also conducted. Six prospective cohort studies were included in the primary meta-analysis. Consumption of coffee was associated with lower risk of cardiovascular mortality (HR=0.70; 95% CI 0.54 to 0.91), I²=0%; 2 studies) and was not associated with an increased risk of all-cause mortality (HR=0.85; 95% CI 0.63 to 1.13; I²=50%; 3 studies), recurrent MI (HR=0.99; 95% CI 0.80 to 1.22; I²=0%; 3 studies), stroke (HR=0.97; 95% CI 0.63 to 1.49; I²=39%; 2 studies) and MACE (HR=0.96; 95% CI 0.86 to 1.07; I²=0%; 2 studies). A significant non-linear inverse dose-response association was found for coffee consumption and all-cause mortality. Conclusions Consumption of coffee was not associated with an increased risk of all-cause mortality and cardiovascular events in patients with previous myocardial infarction.
... Data transformations and imputations were done according to the study protocol, 29 the Cochrane Handbook for Systematic Reviews 32 and following the recommendations of Borenstein et al. 34 Salt intakes in g were transformed to sodium intakes in g by multiplying by 0.4 and sodium intakes in mmol were transformed to sodium intakes in g by multiplying by 0.023. The following imputations were done: when the mean sodium intake or age was missing, the midpoint between the lowest and highest values was used; for the dose-response analysis, when the highest or lowest values of the upper or lower sodium-intake categories were not provided, they were imputed assuming that the sodium-intake range was the same as the adjacent sodium category; 35 if standard errors were not available, they were calculated from standard deviations, confidence intervals (CIs), p-values, t-values, approximated using the Taylor series expansion or imputed as the weighted mean of all standard errors of all studies included in the systematic review. For experimental studies, the effect size was defined as the net difference between the intervention and control groups in the mean change in blood pressure from the baseline to the end of the intervention. ...
Article
Background: High sodium intake is a cause of elevated blood pressure in adults. In children and adolescents, less evidence is available and findings are equivocal. We systematically reviewed the evidence from experimental and observational studies on the association between sodium intake and blood pressure in children and adolescents. Methods: A systematic search of the Medline, Embase, CINAHL and CENTRAL databases up to March 2017 was conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies involving children or adolescents between 0 and 18 years of age were included. Random-effects meta-analyses were performed by pooling data across all studies, separately for experimental and observational studies, and restricting to studies with sodium intake and blood pressure measurement methods of high quality. Subgroup meta-analyses, sensitivity analyses and meta-regressions were conducted to investigate sources of heterogeneity and confounding. The dose-response relationship was also investigated. Results: Of the 6572 publications identified, 85 studies (14 experimental; 71 observational, including 60 cross-sectional, 6 cohort and 5 case-control studies) with 58 531 participants were included. In experimental studies, sodium reduction interventions decreased systolic blood pressure by 0.6 mm Hg [95% confidence interval (CI): 0.5, 0.8] and diastolic blood pressure by 1.2 mm Hg (95% CI: 0.4, 1.9). The meta-analysis of 18 experimental and observational studies (including 3406 participants) with sodium intake and blood pressure measurement methods of high quality showed that, for every additional gram of sodium intake per day, systolic blood pressure increased by 0.8 mm Hg (95% CI: 0.4, 1.3) and diastolic blood pressure by 0.7 mm Hg (95% CI: 0.0, 1.4). The association was stronger among children with overweight and with low potassium intake. A quasi-linear relationship was found between sodium intake and blood pressure. Conclusions: Sodium intake is positively associated with blood pressure in children and adolescents, with consistent findings in experimental and observational studies. Since blood pressure tracks across the life course, our findings support the reduction of sodium intake during childhood and adolescence to lower blood pressure and prevent the development of hypertension.
... 4 In such cases, dose-response trends that are calculated using different methods of assigning values for open-ended categories will reflect the sensitivity of the conclusions. 4 The nonlinear slope was changed in our analysis when using the other methods of exposure assignment for the open-ended categories as reported by Crippa et al. 1 To test the sensitivity of the linear trends in our analysis, we re-analysed the data by setting the highest open-ended category to be the same amplitude as the preceding category. Statistical analyses were conducted using STATA 12.0 (StataCorp, College Station, TX, USA). ...
Article
Full-text available
Existing epidemiological evidence is controversial regarding the possible associations between coffee consumption and risk of prostate cancer (PCa) by aggressiveness of the disease. We conducted a random-effects dose-response meta-analysis to assess the relationships between coffee consumption and nonaggressive, aggressive and fatal PCa risk. Studies were identified by a search of Medline and Embase databases to 15 July 2013. We carried out separate analyses by grade (Gleason score: low-grade, high-grade) and stage (TNM staging system: localized, advanced) of the tumors. Nonaggressive tumors were defined as low-grade or localized, while aggressive tumors were defined as high-grade or advanced. Eight studies (three case-control and five cohort) were included in this meta-analysis. Gleason 7 tumors were classified as high-grade in one study, while in another study, Gleason 7(4 + 3) tumors were classified as high-grade and Gleason 7(3 + 4) as low-grade. In the remaining four studies, Gleason 7 tumors were excluded from the analyses or analyzed separately. The pooled relative risk (RR) for a consumption increment of 3 cups/day was 0.97 [95% confidence interval (CI) 0.92-1.03] for low-grade PCa (n = 6), 0.97 (95% CI 0.94-0.99) for localized PCa (n = 6), 0.89 (95% CI 0.78-1.00) for high-grade PCa (n = 6), 0.95 (95% CI 0.85-1.06) for advanced PCa (n = 6) and 0.89 (95% CI 0.82-0.97) for fatal PCa (n = 4). No evidence of publication bias was observed. Heterogeneity was absent or marginal (I(2) range = 0-26%), with the only exception of the analysis on advanced PCa, where moderate heterogeneity was observed (I(2) = 60%). When restricting the analyses only to those studies that defined high-grade tumors as Gleason 8-10, the inverse association became slightly stronger [RR: 0.84 (95% CI 0.72-0.98); n = 4]. Results from this dose-response meta-analysis suggest that coffee consumption may be inversely associated with the risk of fatal PCa. No clear evidence of an association with PCa incidence was observed.
Article
Full-text available
Background & Aims There is conflicting epidemiologic evidence on whether coffee consumption reduces the risk of gallstone disease. We examined the association between coffee consumption and risk of cholecystectomy (as a proxy for symptomatic gallstone disease) in a prospective cohort study. Methods We collected data from 30,989 women (born 1914–1948) and 40,936 men (born 1918–1952) from the Swedish Mammography Cohort and the Cohort of Swedish Men. Baseline information on coffee consumption was collected using a food-frequency questionnaire; subjects were followed up for procedures of cholecystectomy from 1998 through 2011 by linkage to the Swedish Patient Register. Hazard ratios (HRs) were estimated using Cox proportional hazard models. Results During a total follow-up period of 905,933 person-years, we identified 1057 women and 962 men who had undergone a cholecystectomy. After adjustment for potential confounders, the HR of cholecystectomy was 0.58 (95% confidence interval [CI], 0.44–0.78) for women who drank ≥6 cups of coffee/day compared with women who drank <2 cups/day. In contrast, there was no association in men (HR, 0.96; 95% CI, 0.75–1.24). Because of this sex difference, we examined and found evidence of effect modification by menopausal status and use of hormone replacement therapy (HRT) (Pinteraction=.026). An inverse association was observed only in women who were premenopausal (HR, 0.17; 95% CI, 0.05–0.55) or used HRT (HR, 0.44; 95% CI, 0.28–0.70). Conclusion We observed an inverse association between coffee consumption and risk of cholecystectomy in women who were premenopausal or used HRT but not in other women or in men.
Article
Full-text available
Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity < 0.001). The largest risk reductions were observed for 4 cups/day for all-cause mortality (16%, 95% confidence interval: 13, 18) and 3 cups/day for CVD mortality (21%, 95% confidence interval: 16, 26). Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected] /* */
Article
Epidemiologic evidence on coffee consumption reducing the risk of gallstone disease has been contradictory. To perform a meta-analysis of observational studies, to investigate an association and dose-response of coffee consumption with gallstone disease. We used PubMed and EMBASE databases to identify all published studies before June 2015. A random-effects model was used to compute a pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). One case-control study and five prospective cohort studies (with seven cohorts) involving 227 749 participants and 11 477 gallstone disease cases were included. Coffee consumption was significantly associated with a reduced risk of gallstone disease (RR, 0.83; 95% CI, 0.76 to 0.89; I(2) = 35.9%), based on prospective studies; specifically, we observed an inverse relation in females, but not in males. The case-control study did not reveal any association between coffee and gallstone disease (OR, 0.99; 95% CI, 0.64 to 1.53). In a dose-response analysis, the RR of gallstone disease was 0.95 (95% CI, 0.91 to 1.00; P = 0.049) per 1 cup/day of coffee consumption. A significant nonlinear dose-response association was also identified (P for nonlinearity = 0.0106). For people who drank 2, 4 and 6 cups of coffee per day, the estimated RRs of gallstone disease were 0.89 (95% CI, 0.79 to 0.99), 0.81 (95% CI, 0.72 to 0.92) and 0.75 (95% CI, 0.64 to 0.88), respectively, compared with the lowest level drinkers. This study suggests that coffee consumption is related to a significantly decreased risk of gallstone disease. © 2015 John Wiley & Sons Ltd.
Article
Coffee has several metabolic effects that could reduce the risk of gallstone formation. To examine the association between coffee consumption and the risk of symptomatic gallstone disease in men. The Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996. A total of 46008 men, aged 40 to 75 years in 1986, without history of gallstone disease. Newly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy. During 404 166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend = .005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (< or =25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk. In this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease.
Article
Metabolic studies have shown that coffee affects several hepatobiliary processes that are involved in cholesterol lithogenesis. We previously showed that coffee drinking was associated with a lower risk of symptomatic gallstone disease in men. We prospectively examined the association between coffee drinking and cholecystectomy, a surrogate of symptomatic gallstone disease, in a cohort of 80,898 women age 34-59 years in 1980 who had no history of gallstone disease. Coffee consumption and cholecystectomy were reported by participants on biennial mailed questionnaires. During 20 years of follow-up to the year 2000, 7,811 women reported a cholecystectomy. Compared with women who consistently reported consuming no caffeinated coffee, the multivariate relative risks (adjusting for risk factors for gallstone disease) of cholecystectomy comparing increasing categories of consistent intake of caffeinated coffee (0, 1, 2-3, and > or =4 cups/day) were 1.0, 0.91, 0.78, and 0.72 (95% confidence interval comparing extreme categories, 0.62-0.84; P value of test for trend < 0.0001). Caffeine intake from beverages and dietary sources was also inversely associated with risk of cholecystectomy. The multivariate relative risks comparing increasing categories of caffeine intake (< or =25, 26-100, 101-200, 201-400, 401-800, and >800 mg/day) were 1.0, 1.03, 1.01, 0.94, 0.85, and 0.85 (95% confidence interval comparing extreme categories, 0.74-0.96; P value of test for trend < 0.0001). In contrast, decaffeinated coffee was not associated with risk. These data suggest that consumption of caffeinated coffee may play a role in the prevention of symptomatic gallstone disease in women.
Dosresmeta: performing multivariate doseresponse meta-analysis
  • A Crippa
  • N Orsini
Crippa A, Orsini N. Dosresmeta: performing multivariate doseresponse meta-analysis. Available at: http://CRAN.Rproject.org/package=dosresmeta (accessed 18 September 2015).
Dosresmeta: performing multivariate dose-response meta-analysis
  • Crippaa Orsinin