Study population
The 1995–1997 HUNT (HUNT 2) study covered a wide range of topics in two questionnaires. The first questionnaire (Q1) was enclosed with the invitation letter and completed at home and delivered during attendance at the health examination. Q1 included three questions about caffeine consumption. The second questionnaire (Q2), which also included questions about headache and ergotamine intake, was filled in after the examination and returned by mail. Of the 92,566 invited inhabitants, a total of 51,383 subjects (56%) completed the headache questionnaire [14], whereof 50,483 (55%) answered the question about caffeine consumption. Details of the non-participants are described elsewhere [14, 15].
The study was approved by the Regional Committee for Ethics in Medical Research, and the HUNT Study is also approved by the Norwegian Data Inspectorate.
Estimation of caffeine consumption
The participants were asked to report the number of cups of brew coffee, other types of coffee (i.e. instant coffee and drip coffee), and tea per day. Based on previous data from Norway [16], the estimated caffeine content per cup was 90 mg for brew coffee, 80 mg for other types of coffee, and 50 mg for tea [16]. Headache patients were asked to report the number of ergotamine tablets and suppositories (Cafergot® and Anervan®) used during the past month. The caffeine content for Cafergot was 100 mg, for Anervan suppository 100 mg, and for Anervan tablets 50 mg. The caffeine consumption per day due to use of ergotamine medication was calculated by dividing the total amount of caffeine due to ergotamine intake by 30. Total overall caffeine consumption (mg/day) was the sum of caffeine per day due to brew coffee, other types of coffee, tea, and ergotamine-containing medication.
Information regarding caffeine consumption due to caffeinated soda, hot chocolate, and other caffeine-containing medications (OTC or prescribed) were not available.
Headache diagnosis
The headache questions in Q2 and the prevalence of headache are published elsewhere [14, 15]. The headache questions were designed mainly to determine whether or not the person had headache, and the frequency of headache, and to diagnose migraine according to a modified version of the migraine criteria of the Headache Classification Committee of the IHS [17]. Subjects who answered “yes” to the question “Have you suffered from headache during the last 12 months?” were classified as headache sufferers. Based on data from the subsequent 12 headache questions, they were classified into two groups of either migraine or non-migrainous headache. The diagnoses were mutually exclusive. A headache which did not fulfil the criteria for migraine was classified as a non-migrainous headache. Based on a question about headache frequency during the last year, headache frequency was divided in three categories; <7, 7–14, and >14 days/month.
The classification of the subjects has been described in detail previously, and has been validated by interview diagnoses [18]. In short, for migraine, the positive predictive value (PPV) was 84% and the negative predictive value (NPV) was 78%; for non-migrainous headache, the PPV was 68% and the NPV was 76% [16]. For the questionnaire-based diagnosis of migraine with aura, the PPV and specificity were 100%, whereas the NPV was 91% and sensitivity was 42% [18].
Statistics
Differences between continuous variables were tested with one-way analyses of variance and between proportions by Chi-squared test. In the multivariate analyses, using logistic regression, we estimated the prevalence odds ratio (OR) with 95% confidence interval (CI) for the association between headache and caffeine consumption. The participants were categorized into quartiles based on individual values of total caffeine consumption. High caffeine consumption was defined as the top quartile (>540 mg/day), whereas low caffeine consumption was defined at the low quartile (0–240 mg/day). Separate analyses for dietary caffeine consumption (excluding caffeine due to use of ergotamine-containing medication) were also done. A large number of confounders were evaluated, e.g. current smoking as it reduces the halftime of caffeine with 30–50% [19], and use of oral contraceptives in women because they increase the level of caffeine with as much as 50% [20]. In the final analyses we adjusted for age, gender, smoking, and education level as confounders. Other potential confounding factors like physical activity, previous myocardial infarction, alcohol consumption, body mass index, and mean systolic blood pressure were also evaluated, but were excluded from the final analyses because they changed the OR by <5%. When appropriate, caffeine consumption was also treated as a continuous variable and was incorporated in a two sided test for trend to evaluate the probability of a linear relationship between caffeine consumption and headache. We also investigated potential interaction between age and caffeine consumption by including the product of the two variables into the logistic regression analyses. The interaction coefficient was tested using Wald χ2 statistics. Data analyses were performed with the Statistical Package for the Social Sciences, version 15.0 (SPSS, Chicago, IL, USA).