Mortality and predictors of mortality in rheumatoid arthritis--a role for mannose-binding lectin?
OBJECTIVE
Patients with rheumatoid arthritis (RA) have increased overall and cardiovascular mortality. Mannose-binding lectin (MBL) may play differentiated roles in the pathogenesis of RA. We had observed that high serum levels of MBL increased the risk of ischemic heart disease in patients with RA. In this followup study we describe the mortality in a cohort of 229 Danish patients with RA. We examine if previously reported factors and MBL influence the risk of overall death and death due to cardiovascular disease.


METHODS
Known predictors of RA mortality were assessed. MBL extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) were determined; MBL serum concentrations were measured. The vital status and causes of death were assessed in a prospective study.


RESULTS
The median followup was 10.3 years. The overall risk of death was 4% per year. Comparing mortality in the RA cohort with mortality in an age- and sex-matched cohort based on the general Danish population, we found significantly increased overall mortality [standardized mortality ratio (SMR) 1.5, 95% CI 1.2-1.9, and cardiovascular mortality (SMR 1.7, 95% CI 1.3-2.6)]. In multivariate analysis, significant predictors of overall death were extraarticular manifestations, positive rheumatoid factor, increased C-reactive protein (CRP), poor nutritional state, and serum MBL. Predictors of cardiovascular death were Health Assessment Questionnaire score, increased CRP, poor nutritional state, and the high-producing MBL genotype YA/YA.


CONCLUSIONS
Both overall and cardiovascular mortality were increased in Danish patients with RA. In our cohort, states of high MBL production and several previously reported factors contributed significantly to this increased risk of overall death and cardiovascular death.
Troelsen
Lone N
LN
Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. lone.troelsen@mail.dk
Garred
Peter
P
Jacobsen
Søren
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality*; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics; D037241:Mannose-Binding Lectins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000097:blood; D012307:Risk Factors
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D037241:Mannose-Binding Lectins; D002097:C-Reactive Protein; D012217:Rheumatoid Factor