"This knowledge could facilitate a targeted prevention program for CVD in patients with IP and RA," conclude the researchers led by Tracey M. Farragher, PhD, of the University of Manchester in the UK.
The researchers analyzed the HLA-DRB1 and PTPN22 genes among 1022 patients with IP and 751 with RA along with their interactions with known RA risk factors including SE, smoking, and anticyclic citrullinated peptide (anti-CCP) status. The results were adjusted by patient sex and age at symptom onset.
Available data for each participant included results of blood tests for rheumatoid factor (RF), elevation of C-reactive protein (CRP) and anti-CCP antibodies, evaluations of joint pain and functional disability, smoking habits, and cause and date of death (when applicable) between 1989 and 1994. Researchers also performed HLA-DRB1 and PTPN22 genotyping on every patient's DNA.
Overall, 242 (24%) of the patients died, and CVD was listed as the cause of death for 76 (31.4%) of them. Participants who had 2 copies of the SE alleles had an increased the risk of death from all causes (HR 1.57) and from CVD (HR 1.68). The risk of death from CVD was increased >3-fold for individuals with the HLA-DRB1 combination, the study showed. This was independent of RF and CRP levels, but was aggravated by the interaction of SE, anti-CCP antibodies, and smoking. Specifically, current smokers who carried 2 SE alleles and had anti-CCP antibodies had the highest risk of dying from all causes, as well as a substantially higher risk of dying prematurely from CVD (HR 7.81).
There was no evidence of any association between the PTPN22 gene and the risk of death in these inflammatory arthritis patients.
Translating research into practice
"This is a very good study, which sheds further light on the association of RA and premature mortality and CVD" said Eric Matteson, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota. "It establishes that genes that are strongly associated with RA are also strongly predictive of these cardiovascular risks."
These genes, as well as more disease specific markers like RF and the anti-CCP antibody are severity markers for RA. "Patients with more severe RA have more CVD as well," Dr. Matteson said.
"While one cannot alter one’s genes, knowing about modifiable risk factors especially likely to lead to increased risk of CVD and death is especially important in patients with RA," Dr. Matteson explained. The risk factors include stopping smoking; managing lipids and weight; improving of the patient’s physical activity, capacity, and function; and controlling arthritis inflammation.
Reference
1. Farragher TM, Goodson, NJ, Naseem H, et al. Association of the HLA-DRB1 gene with premature death, particularly from cardiovascular disorder, in patients with rheumatoid arthritis and inflammatory arthritis. Arthritis Rheum. 2008;58:359-369
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