Diet and other environmental factors and the risk of rheumatoid arthritis in a population-based prospective cohort study

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that affects primarily the joints. RA leads to cartilage destruction and bone erosion, with substantial loss of quality of life. RA is associated with an increased risk of cardiovascular disease, osteoporosis, gastrointestinal disorders, thus increasing disability and mortality. RA affects 0.5-1% of the adult population, and is three times more common among women than among men. Twin studies have shown that the relative contribution of genetic factors to RA is about 50%, leaving the remaining part to environmental factors. Few epidemiological studies have examined risk factors for RA. Even though cigarette smoking is an established risk factor for RA, the role of its characteristics in the development of the disease is less clear. In addition, analyses of other risk factors have led to inconclusive and often conflicting results.

Aims of this thesis were: 1) to analyze the association between characteristics of cigarette smoking (intensity, duration and cessation) and RA risk in a population-based prospective cohort study and by summarizing published evidence; 2) to evaluate the association of alcohol consumption and risk of RA; 3) to estimate the dose-response relationship between long-chain n-3 polyunsaturated fatty acids (PUFAs) and risk of RA; 4) to evaluate long-term intake of alcohol and long-chain n-3 PUFAs, as well as the long-term consumption of fish in relation to RA; 5) to prospectively evaluate the association between physical activity and RA.

The data used to assess the association between selected exposures and the development of RA were obtained by means of questionnaires administered in 1987 and 1997 to the Swedish Mammography Cohort. Among the 35 187 women that did not have RA or non-RA joint conditions before the start of follow-up in 2003, 224 developed RA before 2010. Results showed a twofold increased risk among current smokers compared with never smokers, even when their exposure to smoking was low (<7 cigarettes per day). The risk of RA decreased over time following smoking cessation, but remained elevated after more than 15 years since smoking cessation compared with never smokers. Moderate alcohol consumption (a median of 6 glasses of alcohol per week) was associated with a 37% decreased risk of RA. In addition, long-chain n-3 PUFA dietary intake was inversely associated with RA risk, and women with an intake of more than 0.21 grams per day of long-chain n-3 PUFAs had a 35% decreased risk compared with women with a lower intake (≤0.21 grams per day). A consistent moderate long-term intake of both alcohol and long-chain n-3 PUFAs was associated with a halved risk of RA. Long-term consumption of fish was inversely associated with RA, but after adjustment for their content of long-chain n-3 PUFAs the association disappeared. Leisure-time activity (combination of walking and exercising) was associated with a decreased risk of RA.

Results from this thesis showed that modifiable lifestyle factors, including smoking, alcohol consumption, long-chain n-3 PUFAs intake and physical activity, are associated with RA development.

List of scientific papers

I. Di Giuseppe D, Orsini N, Alfredsson L, Askling J, Wolk A. Cigarette smoking and smoking cessation in relation to risk of rheumatoid arthritis in women. Arthritis Res Ther. 2013 Apr 22;15(2):R56.
https://doi.org/10.1186/ar4218

II. Di Giuseppe D, Discacciati A, Orsini N, Wolk A. Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis. Arthritis Res Ther. 2014 Mar 5;16(2):R61
https://doi.org/10.1186/ar4498

III. Di Giuseppe D, Alfredsson L, Bottai M, Askling J, Wolk A. Long term alcohol intake and risk of rheumatoid arthritis in women: a population-based cohort study. BMJ. 2012 Jul 10;345:e4230
https://doi.org/10.1136/bmj.e4230

IV. Di Giuseppe D, Wallin A, Bottai M, Askling J, Wolk A. Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women. Ann Rheum Dis. 2013 Aug 12.
https://doi.org/10.1136/annrheumdis-2013-203338