Rheumatoid arthritis (RA) is a chronic, progressive, systemic, autoimmune disease for which there is no current cure. It is a common disorder affecting more than 2.1 million Americans.

Patients who present with complications of RA outside the joints- what is termed extra-articular disease- are at particular risk for early death. Extraarticular problems that can be seen in RA include, skin ulcers, anemia, eye inflammation, lung inflammation and damage, heart disease, inflammation of blood vessels, and rheumatoid nodules(these are bumps consisting of inflamed tissue that grow at certain areas such as the fingers, elbows, heels, and back of the skull).

A predictor of the presence of extra-articular disease is the level of rheumatoid factor in the blood. The higher the rheumatoid factor, the more likely a patient will have extra-articular disease.

A newer blood marker, the anti-CCP (anti cyclic citrullinated peptide), also appears to predict higher risk of extra-articular problems as well as more severe disease.

The bottom line is that RA is not a benign condition. In fact, it carries the same mortality as first heart attacks, untreated diabetes, and stage 4 Hodgkins disease in some studies. RA must be diagnosed and treated aggressively.

Probably the primary cause of the increased mortality is cardiovascular death. Estimates range from 33-50% of all deaths in RA patients are due to cardiovascular causes. Patients with RA are at significantly increased risk for atherosclerosis, congestive heart failure, heart attack, and vasculitis (inflammation of blood vessels).

So what are some of the risk factors that particularly are important?

Among them are:

Severe RA disease

Severe extra-articular disease

Elevated blood levels of homocysteine which is aggravated by methotrexate therapy

Abnormalities of blood vessel walls

Drugs that are used to treat RA such as corticosteroids and non-steroidal anti-inflammatory drugs

Overproduction of inflammatory cytokines (chemical messengers of disease)

Rheumatoid nodules

A note about drugs...

Methotrexate, the most commonly used disease-modifying anti-rheumatic drug is associated with a significant reduction in the incidence of cardiovascular death. Unfiortuantely, nonsteoridal anti-inflammatory drugs which are commonly used to treat symptoms in RA increase the risk of blood clots, cardiovascular disease, and congestive heart failure.

The role of other medical problems such as blood sugar, elevated lipids, and so forth are a subject for another article.

Recommendations for reduction of cardiovascular risk in RA patients include:

Low dose aspirin (which should be supplemented with some type of stomach protection) particularly in patients who are taking non-steroidal anti-inflammatory drugs.

Statin drugs for people with elevated lipids

Folic acid supplementation to minimize the elevated homocysteine levels seen in RA

Caution with the use of TNF-inhibitors in patients with congestive heart failure

Control of co-morbid conditions such as smoking, diabetes, and hypertension that might aggravate the tendency towards cardiovascular risk.

Complicating this issue is some data showing that TNF inhibitors can elevate serum lipids in some instances. The implications of this phenomenon on the overall picture is still unknown.

A bright note: there is increasing evidence that aggressive treatment with methotrexate and TNF-inhibitors reduces the incidence of cardiovascular events. Therefore, the above-mentioned lipid problem may not be that important. Further studies are obviously needed to confirm these findings.