Methods
Study Population
Study participants were from two cohorts, the HPFS and NHS. The HPFS was established in 1986 when 51 529 male health professionals between the ages of 40 and 75 completed a baseline questionnaire. Information on medical history and lifestyle factors was collected biennially via mailed questionnaires in the two cohorts since baseline. The NHS was established in 1976 when 121 701 married female registered nurses ages 30–55 in the USA completed a baseline questionnaire regarding their medical history and lifestyle risk factors. This study was approved by the Institutional Review Board of Brigham and Women's Hospital. The participants' completion and return of the self-administered questionnaires were considered as informed consent.
Assessment of Exposures (Psoriasis and Psoriatic Arthritis)
In 2008, we queried cohort participants about physician-diagnosed psoriasis and the diagnosis date in the HPFS (before 1986, 1986–1990, 1991–1995, 1996–2000, 2001–2004, and 2005 or later) and NHS (1997 or before, 1998–2001, 2002–2005, 2006–2007 and 2008). We confirmed self-reported psoriasis using the Psoriasis Screening Tool (PST) questionnaire, which inquired about the type of clinicians making the diagnosis and phenotypes. A pilot study showed a sensitivity of 99% and a specificity of 94% for PST in psoriasis screening. Diagnoses of psoriasis with concomitant PsA were confirmed using the psoriatic arthritis screening and evaluation (PASE) questionnaire, which includes a symptom scale with seven items and a function scale with eight items. Women chose one of five categories relating to agreement (strongly agree to strongly disagree) for each item. A total score of 47 or greater has been shown to identify PsA with a high sensitivity and specificity in our pilot studies as well as in cohort PsA diagnosis validation. PASE has good test–retest reliability.
Assessment of Outcome (Gout)
We ascertained incident cases of gout using the American College of Rheumatology gout survey criteria, as previously described. In HPFS, the participants were asked biennially since baseline whether they had received a physician diagnosis of gout and, if so, the date of first occurrence. In the NHS, the participants were asked for diagnoses of incident gout in 1982, 1984, 1986, 1988, 2002, and biennially thereafter. Starting in 2001, we mailed a supplementary questionnaire to participants with self-reported incident gout diagnosed during the follow-up to confirm the report and to ascertain whether the cases met the American College of Rheumatology (ACR) gout survey criteria. The primary end point in this study was incident cases of gout that met 6 or more of the 11 gout criteria (more than one attack of acute arthritis, maximum inflammation developed within 1 day, oligoarthritis attack, redness observed over joints, painful or swollen first metatarsophalangeal joint, unilateral first metatarsophalangeal joint attack, unilateral tarsal joint attack, tophus, hyperuricaemia, asymmetric swelling within a joint, and complete termination of an attack). The overall response rate for the supplementary gout questionnaire was around 80% in both cohorts. Two board-certified rheumatologists reviewed the medical records from a sample of 76 men and 56 women in 2001. Of the76 men, 26 (34%) did not have relevant and complete records. Among the remaining 50 men, the rate of concordance between the diagnosis of gout according to the criteria of the American College of Rheumatology and the diagnosis of gout according to our review of the medical records was 94% (47/50). The concordance rate was similar in women (91%, 51/56).
Covariates
Information on weight, smoking, diuretics use, aspirin use, and personal histories of type 2 diabetes and hypertension, and menopausal status and postmenopausal hormones use (for women) was collected biennially during follow-up. Height was reported at cohort baseline. Body mass index was calculated as weight in kilograms divided by height in m for each follow-up period. Physical activity was assessed biennially in the HPFS and in 1998, 2000, 2004 and 2008 in the NHS. Information on dietary intake was collected using a validated food-frequency questionnaire, and was available in 1986, 1990, 1994, 1998, 2002 and 2006 in the HPFS, and in 1998, 2002 and 2006 in the NHS.
Statistical Analysis
Participants who did not respond to the psoriasis questions in 2008 or self-reported psoriasis that occurred before the baseline were excluded from the analysis. A total of 27 751 men and 71 059 women were included in the present analysis; they contributed person-years of follow-up from the return date of the baseline questionnaire to the diagnosis date of gout or the end of follow-up (1 June 2010), whichever came first. We ensured that the exposure (psoriasis/PsA) occurred before the outcome (gout).
We used Cox proportional hazards analyses to estimate the age- and multivariate-adjusted relative risks (HRs) and 95% CIs for the association between history of psoriasis/PsA and risk of incident gout. Multivariate-adjusted HRs were calculated after adjusting for age, body mass index (BMI), alcohol, physical activity, smoking status, hypertension, type 2 diabetes, diuretics use, aspirin use, and daily average intakes of total vitamin C, coffee, total meats, seafood, total dairy foods and free fructose. All the covariates were updated during follow-up to account for changes over time. For the pooled analysis, we tested the between-study heterogeneity and estimated the overall association from a random-effects model. As a sensitivity analysis, we also examined the association of psoriasis history at baseline (1986 in the HPFS and 1998 in the NHS) and risk of indent gout during the entire follow-up. We further examined the association between history of other inflammatory arthritis (rheumatoid arthritis) and non-inflammatory arthritis (osteoarthritis) and risk of incident gout, and between history of gout and risk of incident psoriasis/PsA. All statistical analyses were performed using SAS V.9.2. All statistical tests were two-tailed, and the significance level was set at p<0.05.