A Study of Multiple Causes of Death in Rheumatoid Arthritis.

OBJECTIVE: To evaluate rheumatoid arthritis (RA)-related mortality in the state of São Paulo (Brazil). METHODS: Data from all death certificates (DC) from 1996 to 2010 were analyzed using a multiple cause-of-death method. We compared the results from 2 subperiods (1996-2000 and 2006-2010). RESULTS: We found 3955 DC related to RA - 27.6% with RA as the underlying cause of death (UCD) and 72.4% with RA as the nonunderlying cause of death (NUCD). Ninety percent of RA-related deaths occurred at age ≥ 50 years. The mean ages at death were 67.1 ± 13.3 and 67.9 ± 13 years for RA as the UCD and NUCD, respectively. The most frequent NUCD associated with RA were pneumonia, sepsis, renal failure, interstitial lung disease, and heart failure. In the last subperiod, there was an increase in infectious causes. When RA was an NUCD, we observed a decrease in the mean age at death for the last subperiod (p = 0.021). The most common UCD were circulatory and respiratory system diseases. Comparing the mean age at death between RA-related deaths and the general population when deaths occurred at ages beyond 50 years, the linear regression analysis showed a downward curve for RA-related death (p < 0.001 and r = -0.795), while for the general population, as expected, the curve had an upward pattern (p < 0.001 and r = 0.993). CONCLUSION: Unexpectedly, RA-related deaths occurred at earlier ages in the more recent subperiod. Cardiovascular disease remained the most important cause, and infectious diseases are an increasing cause of death associated with RA, raising the question of whether infections were related to the more vigorous immunosuppressive treatment recommended by recent guidelines.

High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins.

INTRODUCTION: Takayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) that usually present as granulomatous inflammation in arterial walls. High mobility group box 1 (HMGB1) is a nuclear protein that acts as an alarmin when released by dying or activated cells. This study aims to evaluate whether serum HMGB1 can be used as a biomarker in LVV. METHODS: Twenty-nine consecutive TA patients with 29 healthy controls (HC) were evaluated in a cross-sectional study. Eighteen consecutive GCA patients with 16 HC were evaluated at the onset of disease and some of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. RESULTS: In GCA patients at disease onset mean serum HMGB1 levels did not differ from HC (5.74 ± 4.19 ng/ml vs. 4.17 ± 3.14 ng/ml; p = 0.230). No differences in HMGB1 levels were found between GCA patients with and without polymyalgia rheumatica (p = 0.167), ischemic manifestations (p = 0.873), systemic manifestations (p = 0.474) or relapsing disease (p = 0.608). During follow-up, no significant fluctuations on serum HMGB1 levels were observed from baseline to 3 months (n = 13) (p = 0.075), 12 months (n = 6) (p = 0.093) and at the first relapse (n = 4) (p = 0.202). Serum HMGB1 levels did not differ between TA patients and HC [1.19 (0.45-2.10) ng/ml vs. 1.46 (0.89-3.34) ng/ml; p = 0.181] and no difference was found between TA patients with active disease and in remission [1.31 (0.63-2.16) ng/ml vs. 0.75 (0.39-2.05) ng/ml; p = 0.281]. HMGB1 levels were significantly lower in 16 TA patients on statins compared with 13 patients without statins [0.59 (0.29-1.46) ng/ml vs. 1.93 (0.88-3.34) ng/ml; p = 0.019]. Age was independently associated with higher HMGB1 levels regardless of LVV or control status. CONCLUSIONS: Patients with TA and GCA present similar serum HMGB1 levels compared with HC. Serum HMGB1 is not useful to discriminate between active disease and remission. In TA, use of statins was associated with lower HMGB1 levels. HMGB1 is not a biomarker for LVV.