Page 53 - THE EVOLUTION OF EARLY ARTHRITIS AND CARDIOVASCULAR RISK Samina A. Turk

HOW DOES ESTABLISHED RHEUMATOID ARTHRITIS DEVELOP
The RR of total coffee intake was 1.3 for developing seropositive RA(22). Fourth, much controversy exists about reproductive factors and sex hormone levels in both women
and men in relation to RA. This holds true for menstrual cycle, parity, pregnancy, age
at menopause, hormone use, and male testosterone levels. More recently published 3 articles still show varying results, as also reflected in a recent review(23). A publication
that was not included in this review reported that pregnancy complications, namely preeclampsia, and poor self-rated health during pregnancy were related to a higher risk of later RA(24). Baydoun et al. investigated reproductive history and postmenopausal RA, but only found menopausal age below 40 years to confer the risk of RA after menopause(25). Moreover, no significant relationship could be found between the use of oral contraceptives and the development of RA in two reviews incorporating a total of 28 studies(26). Two other publications produced conflicting results of testosterone levels in men. One did not show a difference between testosterone levels in pre-RA cases versus controls(27) and the other found lower testosterone levels before the diagnosis of RF-negative RA(28). Finally, a recent article publishes information about geographic area and RA incidence, and prevalence and mortality rates(29). Although the focus was more on the burden of disease, the authors do present data showing that RA is more prevalent in Northern countries as compared with countries near the equator.
More focus has been directed lately toward different dietary components and the risk of RA development. Already in 2004 a review suggested the possible role of diet, but it could not quantify the risk(30). Recent publications have focused more on different types of diet. No significant relations could be found for a Mediterranean type diet(31), a carbohydrate-restricted diet(31) and sodium intake (which only led to a significantly increased risk when combined with smoking)(32). Interestingly, sugar-sweetened soda consumption ≥1 serving/day (compared with <1 serving/month) was significantly related to the development of both seropositive and late-onset-seropositive RA (age after 55 years) in women with hazard ratios (HRs) of 1.63 and 2.62, respectively (corrected for other lifestyle components)(33). The amount of added sugar in these drinks may contribute to the pathogenesis of RA by inducing obesity, insulin resistance, and inflammation. In light of the recent rise in obesity prevalence and RA incidence (see subsequently), this might be an important point of interest, and suggests a possibility to intervene in the at-risk subjects.
Most environmental risk factors seem to be more related to seropositive than to seronegative RA. However, obesity was shown to be related mainly to seronegative RA in most publications(5, 34, 35), with only one report also showing a higher risk of ACPA-positive RA in women(36). All underline the importance of obesity as a risk factor. As obesity may be in part related to little exercise, it was hypothesized that regular exercise protects against RA. This was confirmed by two studies which showed regular physical activity indeed leads to less RA, and, if it did occur, patients presented with milder disease(37, 38).
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