Page 56 - THE EVOLUTION OF EARLY ARTHRITIS AND CARDIOVASCULAR RISK Samina A. Turk

CHAPTER 3
Furthermore, adding positive family history of RA to genetic risk models increases the predictive capacity. However, in general, the gene-environment interactions add too little information to the models to be of clinical use(13).
Autoimmunity and biomarkers
Approximately two-thirds of RA patients test positive for RF and/or ACPA at diagnosis, underlying their importance in this disease. Other antibodies preceding and predicting a diagnosis of RA, independent of RF and ACPA status, are anti-carbamylated protein antibodies and anti-peptidyl arginine deiminase type 4 antibodies(6). The discovery of new related autoantibody systems may in the future give more insight into the pathogenesis of RA.
Other blood-based biomarkers such as acute phase reactants or cytokines were not found to have predictive capacity for RA(6).
Clinical prediction models
Quantifying progression to RA with genetic modeling alone is not ready for clinical use, as we have shown earlier. Several studies have taken a different approach by using a combination of clinical characteristics, symptoms, and sometimes imaging findings. The resulting prediction rules are summarized in Table 3. Validation is still needed for all models. With this restriction, they can be useful to inform persons with musculoskeletal symptoms about their risk of arthritis/RA, especially in the presence of RA-related antibodies.
CHANGING INCIDENCE RATES AND MODE OF PRESENTATION OF RA
In 1979, it was hypothesized that RA as a disease entity would disappear eventually (51). Currently, more evidence exists of a pattern of rises and falls over the decades. Over the first half of the 20th century, no data are available. Alamanos et al. summarized studies on incidence and prevalence rates of RA (according to the 1987 American College of Rheumatology (ACR) criteria) from the second half of the 20th century(52). Two out of the three studies, which evaluated time trends of RA occurrence, reported a declining RA incidence of 15% and 47% in 1 and 4 decade(s), respectively (1980-1990 in MN, USA, and 1955-1994 in Finland). In Greece, the incidence remained stable between 1987 and 1995. Studies in Japan and of North American Natives in the USA have also noted a declining incidence of RA(53, 54). The decline in incidence combined with a shift toward higher age at the onset of disease has been attributed to a so-called birth cohort effect(55). This is a term used in social science to describe characteristics of an area of study over time among individuals who are defined by certain early life influences. Following generations will benefit or be harmed by these influences of their ancestors, in this case leading to a decline in RA incidence. However, which specific risk factors would be implicated in the decline of the incidence has not been specified.
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