Scientists have known for some time that people with rheumatoid arthritis are more likely to die prematurely from heart disease than people without RA. One explanation for the arthritis-heart disease connection is that the same inflammatory process that damages joints also damages blood vessels, leading to atherosclerosis. But not all inflammatory diseases carry the same high risk for premature death from heart disease. So researchers at the University of Manchester, England, decided to look at other possible factors – namely two genes, HLA-DRB1 and PTPN22, known to increase RA risk – along with other risk factors.

 In a study of 1,022 arthritis patients, they found that the risk of death from cardiovascular disease was three times greater for individuals with the shared epitope (SE) – a group of HLA-DRB1 alleles with kindred amino acid traits. The risk was independent of rheumatoid factor (an autoantibody common in RA) and C-reactive protein (a protein that signals the presence of inflammation) levels. It was made worse, however, by the interaction of SE, anti-CCP antibodies and smoking. Current smokers who carried two SE alleles and had anti-CCP antibodies had the highest risk of dying from all causes, as well as a much higher risk of dying early from heart disease. Researchers found no evidence of any association between the PTPN22 gene and the risk of death.

This study is the first to link the HLA-DRB1 genotype with premature death, particularly from cardiovascular disease, for those afflicted with any form of inflammatory arthritis, say the study’s authors. They say the results “raise the possibility of a targeted strategy to prevent [heart disease] in these patients.” The results also point out the potentially lethal consequences of smoking; people with arthritis – or those with a genetic predisposition for arthritis – should not smoke.

The study was published in Arthritis & Rheumatism.