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Objective: Previous population studies have suggested that both rheumatoid factor (RF) production and rheumatoid arthritis (RA) may be declining in occurrence, and both secular and birth-cohort influences have been implicated. Since Pima Indians have a very high incidence of RA and also have shown recent evidence of a decline in RA, this study evaluated the relative contributions of age, secular, and birth-cohort influences on RF seropositivity in the Pima Indian population., Methods: RF data, as assayed by both the bentonite flocculation test (BFT) and the sheep cell agglutination test (SCAT), were available on 5,345 Pima Indians born between 1886 and 1975, who were surveyed at biennial intervals between 1966 and 1995. An age-period-cohort analysis was conducted using data on 18,295 examinations undertaken during the period of study., Results: There was a decline in the proportion of positive test results for RF (titer > or = 1:32) by both BFT and SCAT, in both male and female subjects from 1966-1975 to the later decades of the study (1976-1985 and 1986-1995). Across all periods, by both assays, the crude proportion of positive titers increased with increasing age of the subjects. There was a very clear birth-cohort effect: the highest likelihood of seropositivity was in those individuals born around the end of the nineteenth century, with continuing decline in seropositivity up to the most recent birth cohort. A logistic regression analysis, adjusting for Pima heritage and sex, demonstrated a substantially greater influence of birth cohort than of calendar year on the frequency of RF positivity., Conclusion: In the Pima Indian population, environmental influences in early life are important predictors of the lifelong likelihood of RF positivity. This may have implications for understanding the epidemiology and etiology of RA.

Objective: Markers of inflammation have recently been shown to be predictive of cardiovascular disease (CVD). Furthermore, the excess mortality in rheumatoid arthritis (RA), a disease characterized by chronic polyarthritis, is chiefly due to death from CVD. With this background, we studied the effect of inflammation, as reflected by the number of joints with soft tissue swelling, and rheumatoid factor (RF) seropositivity on CVD-related mortality., Methods: Mortality rates and rate ratios for all-cause and CVD-related deaths were computed in a longitudinal, population-based cohort of Pima Indians in Arizona from 1965 through 1994. Repeated health examinations were performed, involving systematic assessment of the features of RA, cardiovascular risk factors, serum titers of RF, as well as mortality. The cohort comprised 4,120 subjects (1,861 men, 2,259 women) who were examined an average of 3.5 times during a mean followup of 14 years., Results: During the followup period, 182 CVD-related deaths ocurred. The age- and sex-adjusted CVD-related mortality rates increased significantly with the presence of a higher number of joints with soft tissue swelling (Ptrend = 0.04), and were 2.07 (95% confidence interval [95% CI] 1.30-3.31) times as high in those subjects who had 2 or more swollen joints as in those who had none. There were no significant additional effects on CVD-related mortality when seropositivity for RF or a previous diagnosis of RA were considered. In age- and sex-adjusted proportional hazards analyses, which were controlled for possible confounders, the effect of swollen joints remained significant (mortality rate ratio 1.33, 95% CI 1.04-1.71 per category increase [no swollen joints, 1 swollen joint, at least 2 swollen joints])., Conclusion: Joint swelling is a significant risk factor for CVD-related death, independent of other known risk factors including a diagnosis of RA. This finding supports the hypothesis that inflammatory mechanisms are important for the development of CVD.

Objective: To describe the clinical features and familial distribution of rheumatoid arthritis (RA) in the Pima Indians., Methods: From 1965 through 1990, all cases of RA as defined by the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 criteria or all cases of seropositive, erosive disease as defined by the Rome criteria were identified in individuals who were age 20 years and older and were of 50% or more Pima/Tohono-O'odham heritage. Radiographs were reviewed by 2 musculoskeletal radiologists who were blinded to case status. Kinship coefficients were used to evaluate familial aggregation., Results: Eighty-eight RA cases were identified from this population-based sample. Over 66% of the cases had seropositive disease, over 60% had erosive disease, and over 40% had subcutaneous nodules. Of the 88 RA cases, 40 were members of families with more than 1 RA case. The remainder were simplex cases., Conclusion: In this population, clinical markers of severe RA were present in a majority of cases. The presence of familial aggregation for RA in the Pima Indians suggests underlying genetic factors in disease pathogenesis.

Objective: To estimate and compare the age- and sex-specific prevalence of radiographic hip osteoarthritis (RHOA) in a population-based study of the Pima Indians, using 3 atlas-based methods for assessing features of RHOA., Methods: Pelvic radiographs from 755 Pima Indians age > or = 45 years enrolled in a population-based study were read using the Kellgren/Lawrence (K/L) grading scale (grade 0-4) and 2 validated individual-radiographic-features (IRF) scales (grades 0-3 for narrowing and osteophytes)., Results: The age- and sex-specific prevalence of RHOA among Pima Indians assessed using the K/L scale was < 10% in all age and sex groups. The prevalence of grade > or = 2 osteophytes assessed using the 2 IRF scales were similar to each other in all age and sex groups. However, differences between the 2 IRF scoring systems were found for the prevalence of grade > or = 2 joint space narrowing., Conclusion: Pima Indians have an age- and sex-specific prevalence of RHOA similar to that found in the US population. Our finding of different joint space narrowing prevalence by the 2 IRF grading scales supports the use of the same atlas-based case definitions for determining disease prevalence for comparative studies.

Objective: To compare the diagnostic properties of the Rome 1961 criteria for active rheumatoid arthritis (RA) and the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria for RA with regard to their ability to classify, diagnose, and predict outcome in RA., Methods: Analysis of cross-sectional and longitudinal data from repeated health examinations and review of clinical records of 3,509 Pima Indians followed up from January 1966 to December 1990., Results: The ACR 1987 criteria identified approximately 50% of the cases identified by the Rome 1961 criteria, in both cross-sectional and longitudinal analyses. The ACR 1987 criteria were better predictors of subsequent development of a clinically supported diagnosis and treatment with slow-acting antirheumatic drugs (both P < 0.001), but were less sensitive than the Rome 1961 criteria for detecting cases for which there already was a clinically supported diagnosis (P < 0.001)., Conclusion: In a population-based analysis, the ACR 1987 criteria are less sensitive for detecting clinical disease, but predict a clinically more severe prognosis, compared with the Rome 1961 criteria. The sensitivity of both sets of criteria to identify clinical disease is improved if multiple examinations or inactive disease are taken into account.

Objective: To evaluate temporal trends in the incidence of rheumatoid arthritis (RA)., Methods: Incident cases of RA were identified among a population-based cohort of Pima Indians in Arizona over the period 1965-1990., Results: Among 2,894 subjects, 78 incident cases of RA were identified. The age-adjusted incidence declined by 55% in men (Ptrend = 0.225), and by 57% in women (Ptrend = 0.017) after controlling for oral contraceptive or estrogen use and for pregnancy experience. During the same period, age-adjusted prevalence rates of active RA decreased by 29% in men (Ptrend = 0.63) and by 40% in women (Ptrend = 0.02). Fewer than 17% of subjects with known RA were taking slow-acting antirheumatic drugs (SAARDs) in 1990., Conclusion: The decrease in incidence and prevalence of RA in this population over such a short period implicates the involvement of an environmental factor(s), other than exogenous estrogens, in the pathogenesis of the disease. However, the possibility that the observed decrease might be explained by an increased use of SAARDs in subjects with RA cannot be excluded.

Objective: To determine the effect of rheumatoid arthritis (RA) on mortality rates., Methods: Longitudinal analyses of data from a cohort of Pima Indians from the Gila River Indian Community in Arizona, who were followed up during the period February 1965 through December 1989., Results: Among 2,979 study subjects aged > or = 25 years, there were 858 deaths, 79 of which occurred in subjects with RA (36 men, 43 women). Age- and sex-adjusted mortality rates were slightly higher in subjects with RA than in those without (mortality rate ratio 1.28, 95% confidence interval [95% CI] 1.01-1.62). Among those with RA, mortality rates were higher in older subjects (mortality rate ratio 1.51 per 10-year increase in age, 95% CI 1.22-1.88), in male subjects (mortality rate ratio 2.23, 95% CI 1.44-3.45, adjusted for age), and in subjects with proteinuria (mortality rate ratio 1.88, 95% CI 1.02-3.46, adjusted for age and sex). Mortality rate ratios for these risk factors were similar in subjects without RA. In addition, among subjects with RA, rheumatoid factor (RF) positivity was predictive of death (mortality rate ratio 1.94, 95% CI 1.10-3.43), and the excess mortality was found primarily among subjects who were seropositive. The death rate from cardiovascular disease (mortality rate ratio 1.77, 95% CI 1.10-2.84) and from liver cirrhosis or other alcohol-related disease (mortality rate ratio 2.52, 95% CI 1.06-6.01) was increased in persons with RA., Conclusion: The results of this population-based study suggest that although the risk of mortality in subjects with RA is significantly higher than in those without RA, the risk ratio is in the lower range of that described previously in studies of clinic-based cohorts. RF positivity as a predictor of early death among subjects with RA indicates that the immunologic processes in seropositive RA may contribute to the events that eventually lead to early death.

Rheumatoid factor (RF) is often detected in subjects who do not have rheumatoid arthritis (RA). To determine if the presence of RF is predictive of the development of RA, 2,712 Pima Indians of Arizona, 20 years of age or older, initially without RA, have been observed for up to 19 years with biennial examinations. These included a medical history, physical examination of the joints, radiographs, and RF determination by sheep cell agglutination test. During the study period, 70 new cases of RA developed. When the population at risk was stratified by RF titer, with reclassification at subsequent examinations if the RF titer changed, the age- and sex-adjusted incidence of RA increased with higher titers of RF. The incidence of RA (in cases per 1,000 person-years) according to RF titer was 2.4 (RF titer less than 1:2); 6.7 (titer 1:2-1:16); 11.0 (titer 1:32-1:256); and 48.3 (titer greater than 1:256) (P less than 0.001). The same trend was also found within each age and sex group, and within groups defined by the number of American Rheumatism Association criteria present before the definite diagnosis. We conclude that the presence of RF, in subjects without RA, is a risk factor for the development of RA, and that this risk is related to the RF titer. It is also suggested that RF may represent a marker of the earliest phases of the pathogenetic process of RA, that may be detectable before the appearance of other features that permit a clinical diagnosis.