Abstract 683: Do autoantibodies predict cardiovascular events and mortality in the general population?
Authors
K. P. Liang, H. M. Kremers, C. S. Crowson, T. M. Therneau, V. L Roger, S. E Gabriel.
Background
The authors have previously reported, upon examination of a single-institution cohort, that rheumatoid factor positivity is predictive of cardiovascular morbidity and mortality. They now undertake to demonstrate whether serologic positivity for CCP antibody as well as ANA, in addition to RF, confer an increase in risk of cardiovascular disease and of mortality in a community-based population.
Methods
Utilizing a single community population-based based cohort study, the investigators identified all community residents who were tested for ANA and RF between the dates of 1/1/1990 and 1/1/2000, as well as those tested for CCP antibody between 9/1/2003 and 1/1/2005. All participants were followed longitudinally until 4/1/2007. Survival analysis techniques were used, with adjustment for age, sex, calendar year and for the presence of a known rheumatic disorder, to quantify the relationship of these three serologic parameters to the outcomes of myocardial infarction, heart failure, and other vascular diseases, as well as mortality was studied.
Results
Among 6547 residents who underwent RF testing, 672 were seropositive. Similarly, 2340 of 8137 studied residents were seropositive for ANA. Finally, 43 residents were seropositive for CCP among 296 who underwent CCP testing. The authors found that in adjusted analyses, RF was predictive of all four outcomes studied. Though the risk of cardiovascular morbidity was elevated for CCP antibody as well, this relationship alone was not statistically significant.
Conclusions
The authors conclude RF and ANA are both predictors of cardiovascular disease and of mortality in the general population. They are also intrigued in that seropositivity for these autoantibodies confers an excess in risk even after adjustment for the presence of a rheumatic disease.
Editorial Comment
Whereas it is known that RF positivity is predictive of a more severe course and of more severe prognosis in those with underlying rheumatoid arthritis, it is intriguing that RF positivity in the general population, a population which would presumably include though persons without an underlying rheumatic disorder, also demonstrated a relationship of the antibodies RF and ANA to cardiovascular morbidity and to mortality. We are not informed, however, what proportion of those studied for RF, ANA and CCP, had an underlying rheumatic disorder. One would presume that these serologies were obtained, in the clinical stetting, because of the suspicion of the treating clinician that an active rheumatic disorder might be operative.
It would also be of interest to know what causes of death were predicted by seropositivity to the studied autoantibody? It is conceivable that seropositivity would confer an increase in risk of neoplastic and infectious causes of mortality in addition to cardiovascular mortality. Though the relationship of CCP to outcomes was not statistically significant, the observed relationship [with a relative risk of 3.2] is still of interest and was likely limited in power given that only 43 residents of the community were positive for CCP. The authors acknowledge that separate study is necessary to determine how seropositive for RF, ANA and possibility CCP antibody are mediating the development of atherosclerosis in affected seropositive persons.
