Nurses’ Health Study Continues to Offer Valuable Patient Data

Questionnaires are very detailed and, in past years, have included photographs of different types of cigarettes and oral contraceptives so nurses could provide specific answers about their use of these products, says Dr. Costenbader.

The study’s deep reserves of detailed information have enabled project after project for Dr. Karlson, who started using these data as a rheumatology fellow in the early ’90s. About 10 years ago, she became interested in the effects of hormonal genes on RA risk. “I wanted to find out how hormones interact with genes to give someone protection against disease. Then I got interested in predicting biomarkers in RA,” she says. She looked for blood samples from the cohort and examined levels of inflammatory cytokines, such as tumor necrosis factor alpha and interleukin 6. “We found significant elevations of these prior to the onset of RA, even up to 12 years before.”

The Nurses’ Health Study provides a map for researchers to follow throughout years of a woman’s life, so they can track what environmental triggers may happen along the way to a rheumatic disease diagnosis, says Dr. Karlson.

“A person is at risk for rheumatoid arthritis. Her immune system is activated, but not enough for her to have symptoms. At some point, a switch is flipped. She starts getting symptoms. But we don’t know what flips that switch,” she says. The cohort’s deep mine of data may help her and other investigators establish the paradigm of RA’s etiology at last, she hopes. “We need a large number of cases to show trends. There is the effect of one factor, and then we have to adjust for others.”

A woman diagnosed with RA at 50 may have reported daily smoking and coffee drinking for the previous 20 years, Dr. Karlson says. “Is caffeine a risk factor for RA? Coffee drinkers tend to be smokers also. The causal factor is smoking, not coffee.”

RA Risk Calculation

In the Nurses’ Health Study’s second phase, respondents reported more exercise, less smoking and less use of post-menopausal hormones, says Dr. Costenbader. “There are still quite a few people who smoke,” she adds.

Dr. Costenbader

These investigators are also looking at women’s dietary habits over the years to spot links to disease risk, says Dr. Karlson. People in Greece seem to have lower RA rates, but it’s unclear if the popular Mediterranean diet may protect North American women from RA. “Is it the high amounts of fish they eat? We have been looking at different kinds of fish, and whether omega-3 fats reduce inflammation,” she says. Eating a fish-rich diet may lower RA risk, but investigators are not yet sure the fish is the protective factor, she says. The Nurses’ Health Study’s broad range of data on diet and lifestyle may one day identify a protective amino acid or lipid, she adds.

“What’s nice is that we have repeated measures in the study. It’s good to see how things change over time. We see if someone smokes and then see when she quits. We see how dietary patterns affect RA risk,” Dr. Karlson says. “These are called time-varying covariates. We can much more precisely see the effects of these factors every two years.”