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Adherence to a healthy lifestyle contributed to lowering the risk for the development of systemic lupus erythematosus (SLE), an analysis of data from the Nurses' Health Study found.

In a multivariable analysis, a higher Healthy Lifestyle Index Score (HLIS) was associated with a decreased likelihood for developing SLE, with a hazard ratio of 0.81 (95% CI 0.71-0.94, P=0.004) per unit increase, according to May Y. Choi, MD, of Harvard Medical School in Boston, and colleagues.

A higher HLIS also was linked with a lower risk for having the severe subtype of SLE in which patients are seropositive for anti-double-stranded (ds) DNA antibodies, with a hazard ratio of 0.78 (95% CI 0.63-0.95, P=0.016), they reported in .

SLE is thought to result from an interaction between genetic and environmental factors such as exposure to cigarette smoke, ultraviolet light, and silica, as well as hormonal and metabolic factors including obesity.

Previous studies have suggested that individual lifestyle factors may contribute to the development of other autoimmune diseases, such as rheumatoid arthritis, and that an overall healthier lifestyle helped lower the risk for multiple chronic diseases including cancer, diabetes, cardiovascular, and autoimmune diseases.

To explore the effects on SLE risk specifically by analyzing the effects of high versus low HLIS, a combination outcome that requires meeting recommended guidelines for diet, exercise, body weight, smoking, and moderate alcohol use, Choi's group analyzed data from the Nurses' Health Studies I and II, which were initiated in 1976 and 1989, respectively.

Participants completed biennial questionnaires on lifestyle, healthy behaviors, and newly diagnosed diseases throughout follow-up. The HLIS was calculated (0 to 5) with one point each being assigned for low-risk behaviors of never/past smoking, not being overweight, drinking alcohol in moderation, following a healthy diet, and exercising regularly.

The study population included 185,962 female nurses. During 4,649,477 person-years of follow-up, 203 new cases of SLE were reported, with 96 being anti-dsDNA positive. Mean age at baseline was 43, and 93% were white. The SLE diagnosis occurred at a median duration of 10.8 years after study enrollment.

The mean HLIS was 1.4.

Compared with women who had only one or no healthy behaviors, those with at least four healthy behaviors had the lowest risk for SLE (HR 0.42, 95% CI 0.25-0.70) and also for anti-dsDNA positive SLE (HR 0.35, 95% CI 0.17-0.75).

This high level of healthy behaviors also was calculated to represent almost half the population attributable risk for SLE (47.7%, 95% CI 23.1-66.6), based on the statistical assumption that the entire study population had at least four healthy behaviors.

The researchers also analyzed the risks using an SLE-specific HLIS, which included only those behaviors that have been clearly linked with SLE (cigarette smoking, moderate alcohol use, and BMI). This subanalysis included 283 cases of SLE and 5,815,211 person-years of follow-up, and found these SLE risks per unit increase in HLIS:

• SLE overall risk: HR 0.75 (95% CI 0.64-0.88)
• dsDNA positive SLE: HR 0.67 (95% CI 0.53-0.85)
• dsDNA negative SLE: HR 0.82 (95% CI 0.67-1)

Using this SLE-specific HLIS, the population attributable risk for SLE was 43.4% (95% CI 17.4-63.8).

Previous studies have examined the influence of individual risk factors such as smoking and obesity on SLE. However, "the approach of studying multiple lifestyle factors together rather than individually provides a more pragmatic and holistic understanding of how lifestyle factors can affect risk of disease events," the authors observed.

They also noted that environmental exposures may influence common pathways associated with disease pathogenesis, "including induction of oxidative stress, damage to endogenous proteins and DNA, autoantibody production, and upregulation of proinflammatory cytokines to induce epigenetic changes, resulting in altered gene expression affecting immune homeostasis," they wrote.

A study limitation was the predominantly white female population, which does not reflect multiple social determinants of health such as poverty, stress, and pollution, so the results will need to be validated in more diverse cohorts, they noted.

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