The graphs show that the and birth cohorts had unusually high incidence rates in their eighth decade of life, and in women of the cohort, there was a high incidence in the seventh decade. Examining successive birth cohorts, the incidence rates for RA fell progressively in both men and women in all age groups.
This is consistent with the previously observed decline in incidence rates over time. The generalized linear models analysis examining the incidence of RA showed that calendar year, age, and sex were significantly related to the incidence of RA Table 4. The apparent change in the male: Survival in this cohort was significantly lower than that in the general population, with a standardized mortality ratio of 1.
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Death certificate information was available on of the patients who had died at the end of the followup period Of these, cardiovascular disease was listed as the primary cause of death in Together, these analyses demonstrated no evidence of change in survival over time. Our findings show a definite and statistically significant progressive decline in the incidence of RA over the study period, — We also found a difference in the age distribution between men and women and an apparent cyclical variation in disease incidence over time.
This is, in large part, due to the inclusion of the 18—35 age group in the present study. The incidence in this age group, which was excluded from the previous study, is considerably lower than that in older groups. The overall incidence rate reported here The rate we report for women during the most recent time period However, the rate we report for men The reason for this difference in incidence rates in men is unclear and may simply reflect random error associated with the relatively small number of men with RA in both studies.
Our finding of a progressive decline in RA incidence over time, affecting both men and women, has been documented in a number of populations over the last few decades. This finding was first reported in a study performed in this center more than 20 years ago Since then, a similar decline has been noted in other US populations 11 , as well as in the UK 12 , 13 and Finland 8.
We performed a birth cohort analysis to examine whether the reduction in RA incidence over time might be partly explained by year of birth. Such analyses have been shown to be useful for elucidating possible etiologic mechanisms in other chronic diseases 15 - We observed a relatively high incidence of RA in individuals born in the latter years of the nineteenth century that progressively declined over subsequent birth cohorts. The only other study in recent years in which a birth cohort analysis was performed found a contrasting pattern, with peak incidence in women occurring in later birth cohorts from to Both analyses do, however, show a progressive decline in RA incidence through more recent birth cohorts.
These trends in incidence over time and through successive birth cohorts are likely to be explained by changing exposure to some environmental factor or factors. Such an environmental factor may take the form of a decline in exposure to some factor that promotes the development of RA or, alternatively, an increase in exposure to a protective factor. The declining incidence rate in women, along with the frequent use of exogenous estrogens for contraceptive and hormone replacement purposes since the s, led to the suggestion that exogenous estrogens might be a protective factor 10 , A number of cohort and case—control studies examining this question have been performed, but the results have been inconsistent A possible hormonal influence is also suggested by the differing age distributions in men and women, which has also been noted in studies from the UK and Finland 9 , The temporal and cyclical pattern we observed in the incidence of RA is consistent with an infectious etiology, since this pattern could reflect the cyclical change in the epidemicity of an infectious disease.
Although a recent study found no evidence of time or seasonal clustering of incident cases as would be expected with a viral etiology, an endemic agent with a latent period between exposure and disease could be responsible for the development of RA in genetically susceptible individuals It is interesting to note that the incidence of and mortality from certain infections in the general population, for example, tuberculosis, dramatically declined in the earlier half of the last century.
Thus, the later birth cohorts in this study are considerably less likely to have been exposed to such infectious diseases. However, it is unclear how an infection would cause RA incidence rates to peak in men and women at different times.
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An infectious etiology for RA has been extensively sought, but no causative microorganism has, as yet, been identified We did not find evidence that the proportion of patients with RF positivity or erosive changes on radiographs had diminished over time. This is in contrast to the findings of 2 previous studies 8 , One of these studies reported that the severity of RA, as measured in terms of RF, rheumatoid nodules, and radiographic erosions, is declining It should be noted, however, that the 3 factors used as severity markers in that study are included in the ACR criteria for RA.
Thus, if the severity of RA were diminishing, and these features were becoming less common in RA patients, patients with inflammatory arthritis would be less likely to fulfill the criteria for RA. This could, in turn, contribute to a decline in RA incidence rates. This finding concurs with previous findings that survival in patients with RA has not improved in recent years, despite significant advances in treatment 24 , It has been suggested that the apparent decline in incidence may reflect changes in diagnostic practice, with the application of more rigid criteria over time.
While selection bias is a possible limitation, it is expected to be minimal in this study because all incident cases of RA diagnosed in the study population during the period of interest have been ascertained through a medical record linkage system. Although use of such a system for case ascertainment has the limitation that RA cases that do not come to medical attention may have been missed, this pattern is unlikely to have changed over time and would not explain the variation in incidence rates over time.
Moreover, we believe that all cases of RA are likely to come to medical attention. Another potential limitation relates to the intensity of testing for RF and bony erosions. It is possible that patients with RA incidence in earlier years had blood tests and radiographs performed less often and that this may have masked a true decline in the prevalence of RF and bony erosions. As a result of the introduction of a privacy law in Minnesota in , one of the original cohort of cases was excluded from the present study and 85 histories from among 2, potential subjects were not available for screening because these individuals had refused authorization for research.
This is unlikely to have significantly affected the incidence rate, since the number of RA cases resulting from screening these extra histories would not have been expected to exceed a total of 8. In conclusion, we have demonstrated sharp and progressive declines in the incidence of RA in a US population over the last 4 decades. These findings point to the need for additional research into the role of environmental, infectious, and hormonal factors in the etiology of this disease.
Volume 46 , Issue 3.
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Michele F. Gregory R. Cynthia S. Sherine E. Gabriel Corresponding Author E-mail address: First published: Tools Request permission Export citation Add to favorites Track citation. Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article.
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