Prescription medication use and antinuclear antibodies in the United States, 1999-2004.

BACKGROUND: Clinical reports link specific medications with the development of antinuclear antibodies (ANA), but population-based evidence is limited. OBJECTIVE: The present study investigated associations between prescription medication use and ANA in a representative sample of the adult noninstitutionalized US population, first focusing on medications previously related to ANA and then considering all medications reported in the National Health and Nutrition Examination Survey (NHANES). METHODS: Based on NHANES data (1999-2004) for 3608 adults (ages ≥18 years), we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess associations between recent medication use and ANA (overall and in sex and age subgroups), adjusted for potential confounders and the survey sampling design. RESULTS: We found no evidence that most medications previously associated with ANA in specific individuals were risk factors for ANA in the general population, although statistical power was limited for some medications. Overall, ANA were less prevalent in adults who recently used any prescription medications compared with those who did not (OR = 0.73; CI = 0.57,0.93), and likewise several classes of medications were inversely associated with ANA, including hormones (OR = 0.73; CI = 0.55,0.98), thiazide diuretics (OR = 0.43; CI = 0.24,0.79), sulfonylureas (OR = 0.41; CI = 0.19,0.89), and selective serotonin reuptake inhibitor antidepressants (OR = 0.65; CI = 0.42,0.98). Positive associations with ANA were seen for loop diuretics (OR = 1.72; CI = 1.03,2.88) in all adults, and for benzodiazepines (OR = 2.11; CI = 1.09,4.10) and bronchodilators (OR = 1.83; CI = 1.00,3.38) in older (ages ≥60) adults. Estrogens were positively associated with ANA in older women (OR = 1.80; CI = 1.00,3.23) but inversely associated with ANA in younger (ages 18-59) women (OR = 0.43; CI = 0.20,0.93). Regarding individual medications, ANA were positively associated with ciprofloxacin (OR = 4.23; CI = 1.21,14.8), furosemide (OR = 1.79; CI = 1.09,2.93), and omeprazole (OR = 2.05; CI = 1.03,4.10) in all adults, and with salmeterol (OR = 3.76; CI = 1.66,8.52), tolterodine (OR = 6.64; CI = 1.45,30.5), and triamterene (OR = 3.10; CI = 1.08,8.88) in older adults. Also, in younger adults, hydrochlorothiazide was inversely associated with ANA (OR = 0.44; CI = 0.20,0.98). CONCLUSIONS: Our findings in the general population do not confirm most clinically reported positive associations between specific medications and ANA in some individuals. However, novel positive ANA associations with other medications, as well as unexplained inverse associations with certain classes of medications and overall medication use, deserve further research to clarify the possible roles of medications as risk and protective factors in the development of autoantibodies and autoimmune disease.

Calcium and vitamin D supplementation and incident rheumatoid arthritis: the Women's Health Initiative Calcium plus Vitamin D trial.

To determine whether calcium plus vitamin D supplementation (CaD) affects incidence of rheumatoid arthritis (RA). Participants enrolled in the Women's Health Initiative CaD trial (n = 36,282) were randomized to 1,000 mg calcium carbonate plus 400 IU of vitamin D(3) daily or to placebo. Incident RA cases were identified via self-report and validated rheumatic medication use. Cox proportional hazards models were used to compare RA incidence in the treatment versus placebo groups. The analysis included 32,435 women without the history of RA, of which 163 incident RA cases were identified over an average of 5.1 years. No significant differences in demographics, total personal vitamin D intake [P = 0.36], or solar irradiance [P = 0.68] were seen between the groups. In intention-to-treat analyses, no differences were observed in RA incidence [HR 1.04, 95% CI 0.76, 1.41]. No significant modifying effects were seen for stratum of age, solar irradiance, or total vitamin D intake, overall or when adjusted for adherence. Significant effect modifications were seen between CaD and total vitamin D intake and CaD and solar irradiance that suggest increased RA incidence with high vitamin D exposure. CaD supplementation did not demonstrate a significant effect on RA incidence in postmenopausal women. Modifying effects between CaD and both solar irradiance and dietary vitamin D intake are suggestive that multiple high vitamin D exposures may increase RA incidence. Further research is needed to fully explore the benefits and possible adverse effects of vitamin D supplementation on RA.

Multivitamin use and telomere length in women.

BACKGROUND: Telomere length may be a marker of biological aging. Multivitamin supplements represent a major source of micronutrients, which may affect telomere length by modulating oxidative stress and chronic inflammation. OBJECTIVE: The objective was to examine whether multivitamin use is associated with longer telomeres in women. DESIGN: We performed a cross-sectional analysis of data from 586 early participants (age 35-74 y) in the Sister Study. Multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire, and relative telomere length of leukocyte DNA was measured by quantitative polymerase chain reaction. RESULTS: After age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres. Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend = 0.002). In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Furthermore, intakes of both nutrients were associated with telomere length among women who did not take multivitamins. CONCLUSION: This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women.

Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: a population-based, case-control study in the southeastern United States.

OBJECTIVE: Crystalline silica may act as an immune adjuvant to increase inflammation and antibody production, and findings of occupational cohort studies suggest that silica exposure may be a risk factor for systemic lupus erythematosus (SLE). We undertook this population-based study to examine the association between occupational silica exposure and SLE in the southeastern US. METHODS: SLE patients (n = 265; diagnosed between January 1, 1995 and July 31, 1999) were recruited from 4 university rheumatology practices and 30 community-based rheumatologists in 60 contiguous counties. Controls (n = 355), frequency-matched to patients by age, sex, and state of residence, were randomly selected from driver's license registries. The mean age of the patients at diagnosis was 39 years; 91% were women and 60% were African American. Detailed occupational and farming histories were collected by in-person interviews. Silica exposure was determined through blinded assessment of job histories by 3 industrial hygienists, and potential medium- or high-level exposures were confirmed through followup telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. RESULTS: More patients (19%) than controls (8%) had a history of medium- or high-level silica exposure from farming or trades. We observed an association between silica and SLE (medium exposure OR 2.1 [95% CI 1.1-4.0], high exposure OR 4.6 [95% CI 1.4-15.4]) that was seen in separate analyses by sex, race, and at different levels of education. CONCLUSION: These results suggest that crystalline silica exposure may promote the development of SLE in some individuals. Additional research is recommended in other populations, using study designs that minimize potential selection bias and maximize the quality of exposure assessment.