Background/Purpose: While the association between lifestyle factors such as alcohol consumption, smoking, and body mass index (BMI) and risk of SLE have been previously investigated, it is unclear how these behaviors may combine to reduce SLE risk. We prospectively evaluated whether a healthy lifestyle was associated with the risk of incident SLE and its subtypes, dsDNA positive (+) versus dsDNA negative (-) SLE. We hypothesized that greater adherence to a healthier lifestyle would be inversely associated with SLE risk.

Methods: We included 217,623 female nurses in the Nurses’ Health Study (NHS) (1976-2016) and NHSII (1989-2017). Lifestyle and environmental were collected at baseline and on subsequent biennial questionnaires. Incident SLE was confirmed by medical record review. Healthy Lifestyle Index Score (HLIS) was calculated at baseline and approximately every 4 years in follow-up, using three lifestyle behaviors: alcohol consumption, BMI and smoking. For each factor, we created a binary low risk or healthy variable, defined as drinking alcohol in moderation (5g-15g/day), normal body weight (BMI 18.5–24.9 kg/m²), and never or past smokers (quit >4 years), each previously associated with reduced SLE risk. A time-varying Cox hazards regression model estimated hazard ratios (HRs [95% confidence intervals]) for SLE risk, overall and by dsDNA subtype. The HLIS was modeled both categorically and continuously for number of healthy behaviors. We also calculated the partial population attributable risk (PAR%), an estimate of the percentage of incident SLE cases in this population during follow-up that would not have occurred if all participants had been in the lowest risk HLIS group (3 healthy behaviors).

Results: There were 283 incident SLE cases (120 anti-dsDNA positive and 163 anti-dsDNA negative) during 5,815,233 person-years of follow-up. In multivariable-adjusted models, we found that a higher continuous HLIS score was associated with a lower SLE risk overall (HR 0.75 [95%CI 0.64-0.88]) and both dsDNA subtypes (positive HR 0.67 [95%CI 0.53-0.85] and negative HR 0.82 [95%CI 0.67-1.00]) (Table). Women with all 3 healthy SLE behaviors had the lowest risk (overall HR 0.45 [95%CI 0.24-0.85] and dsDNA-positive HR 0.39 [95%CI 0.16-0.94]) of developing SLE compared to women with no healthy behaviors. Women who consumed moderate amounts of alcohol had a lower risk of developing SLE overall compared to those who consumed less alcohol (HR 0.62 [95%CI 0.46-0.83]). In addition, women who were never and past smokers were less likely to develop anti-dsDNA positive SLE (HR 0.55 [95%CI 0.36-0.85]) compared to current smokers and those who quit within last 4 years. PAR% revealed that 43.7% of SLE risk in this cohort could be attributable to healthy behaviors not in the lowest risk HLIS group.

Conclusion: Adherence to a healthy lifestyle was associated with a lower risk of SLE development overall and by dsDNA subtype compared to less healthy lifestyle. A larger reduction in risk was seen with each additional healthy behavior. Over 43% of SLE risk could be reduced if everyone had adhered to all three healthy lifestyle behaviors.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-combination-of-healthy-lifestyle-behaviors-reduce-risk-of-incident-systemic-lupus-erythematosus-in-the-nurses-health-studies/