HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis.
OBJECTIVE
Cardiovascular (CV) disease is the most common cause of mortality in patients with rheumatoid arthritis (RA). We assessed the contribution of epidemiologic features, clinical features, routine laboratory markers of inflammation, and HLA-DRB1 alleles to CV mortality in patients with RA prospectively followed at a single referral center in Spain.


METHODS
Patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo between March and September 1996 were included. HLA-DRB1 phenotype, epidemiologic data, and clinical data were assessed at that time. Patients were prospectively followed and clinical records were examined until patient's death or September 1, 2005.


RESULTS
A total of 182 consecutive patients were assessed. Compared with the general Spanish population, the age- and sex-standardized mortality ratio by CV cause was 1.78. CV mortality adjusted by age at disease onset and sex was associated with chronic inflammation determined by C-reactive protein level (CRP; hazard ratio [HR] 1.14, P < 0.001) and erythrocyte sedimentation rate (ESR; HR 1.05, P = 0.003). Patients with HLA-DRB1*04 shared epitope alleles (HR 4.15, P = 0.030), in particular those HLA-DRB1*0404 positive (HR 6.65, P = 0.002), had increased risk of CV mortality. Increased risk of CV events was also associated with CRP level (HR 1.09, P = 0.001), ESR (HR 1.03, P = 0.003), and HLA-DRB1*0404 (HR 4.47, P = 0.002).


CONCLUSIONS
Our results suggest that a chronically high inflammatory response in genetically predisposed individuals promotes an increased risk of CV events and CV mortality in RA.
Gonzalez-Gay
Miguel A
MA
Hospital Xeral-Calde, Lugo, Spain. miguelaggay@hotmail.com
Gonzalez-Juanatey
Carlos
C
Lopez-Diaz
Maria J
MJ
Piñeiro
Angela
A
Garcia-Porrua
Carlos
C
Miranda-Filloy
Jose A
JA
Ollier
William E R
WE
Martin
Javier
J
Llorca
Javier
J
D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics / Q000502:physiology*; D059811:HLA-DRB1 Chains; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013030:Spain
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D002097:C-Reactive Protein