Nearly half of systemic lupus erythematosus risk may be reduced by healthy lifestyle

Healthy lifestyle behaviors could potentially reduce the risk for systemic lupus erythematosus by nearly half, according to data published in Arthritis & Rheumatology.

“A complex interplay between genetic factors and environmental exposures are thought to ultimately lead to autoimmunity in SLE,” May Choi, MD, FRCPC, of Brigham and Women’s Hospital, in Boston, and the University of Calgary, in Alberta, Canada, and colleagues wrote. “About 5{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} to 12{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} of subjects with a first degree relative with SLE will develop SLE in their lifetime, whereas SLE will develop in up to 90{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} of persons with a congenital deficiency of the complement component C4.”

“Environmental exposures such as ultraviolet light, medications, infectious agents, silica, cigarette smoke, alcohol, hormonal factors and obesity have been hypothesized to be associated with SLE development, although the strength of these associations varies,” they added. “The joint impact of multiple healthy behaviors and maintaining healthy body weight on the prevention of SLE development has not been assessed.”

To analyze whether healthy lifestyle factors are associated with a lower risk for SLE and its subtypes — such as anti-double stranded DNA (dsDNA) positive or negative — Choi and colleagues conducted a prospective study of data from the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII). Established in 1976, the NHS included a total of 121,700 married female registered nurses aged 30 to 55 years from 11 U.S. states, while NSHII, developed in 1989, enrolled 116,430 married female registered nurses aged 25 to 42 years from 14 states.

May Choi

For their own study, Choi and colleagues excluded survey participants with SLE or other connective tissue diseases at baseline. In all, the researchers included 96,240 participants from the NHS, followed from 1986 to 2016, and 105,460 from NHSII, followed from 1991 to 2017. As part of the surveys, researchers calculated the Healthy Lifestyle Index Score (HLIS) for each participant at baseline, and approximately every 2 years subsequently in follow-up, based on five factors: Alcohol use, BMI, smoking, diet and exercise.

Low-risk behaviors were identified as never and past smoking, defined as quitting more than 4 years prior; maintaining health body weight, defined as a BMI of less than 25 kg/m²; moderate alcohol exposure, defined as at least 5 g per day; healthy diet; and regular exercise, described as at least 19 metabolic equivalent hours per week or at least 30 minutes of brisk walking every day.

Choi and colleagues used a time-varying Cox hazards regression model to estimate adjusted hazard ratios for SLE risk. They also calculated the partial population attributable risk (PAR{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021}) for SLE development. The final analysis included a total of 185,962 participants from both surveys, with 203 cases of SLE — 96 anti-dsDNA positive and 107 anti-dsDNA negative — across 4,649,477 person-years of follow-up.

According to the researchers, higher HLIS was associated with a lower risk for SLE overall (HR = 0.81; 95{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} CI, 0.71-0.94) and for dsDNA positive SLE specifically (HR = 0.78; 95{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} CI, 0.63-0.95). Participants who demonstrated four or more healthy lifestyle factors demonstrated the lowest risk for SLE overall (HR = 0.42; 95{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021}CI, 0.25-0.70) and dsDNA positive SLE (HR = 0.35; 95{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} CI, 0.17-0.75), compared with those who reported one or zero. The PAR{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} for SLE from adhering to four or more healthy behaviors was 47.7{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} (95{e32b4d46864ef13e127a510bfc14dae50e31bafd31770eb32fd579b90b39f021} CI, 23.1-66.6), the researchers wrote.

“For the first time, we’ve shown that having a healthy lifestyle — a combination of several healthy behaviors — may significantly lower someone’s risk of developing lupus,” Choi told Healio Rheumatology.

In their study, Choi and colleagues wrote: “We found an inverse association between a combination of healthy lifestyle behaviors and SLE risk, associated with nearly half of the population attributable risk.”

“Our findings have implications for SLE prevention and the promotion of multiple lifestyle behaviors to derive the greatest benefit,” they added. “We also provided further insight into the pathogenesis of SLE as a greater than expected proportion of SLE risk may be attributable to modifiable lifestyle factors.”