Combined healthy lifestyle score and odds of rheumatoid arthritis in Iranian adults: a nested case–control from PERSIAN Dena Cohort Study (PDCS)
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* Javad Harooni
* Abdollah Pourjavid
* Farshad Amirkhizi
* Soudabeh Hamedi-Shahraki
* Fatemeh Kiani
* Mohammad-Amin Zolghadrpour
* Vahid Monfared
* Somayyeh Asghari
* Mohammad-Reza Jowshan

## Abstract

**Objectives** Lifestyle factors play a significant role in the development of chronic diseases. While researchers have extensively studied individual lifestyle components, the combined impact of multiple lifestyle factors on rheumatoid arthritis (RA) remains unclear. This study aimed to explore the association between a Combined Healthy Lifestyle Score (CHLS) and the odds of developing RA among Iranian adults.

**Design** A nested case–control study.

**Setting** The study was conducted in Dena County (Sisakht region) near Yasuj city, Iran, as part of the PERSIAN Cohort Study.

**Participants** 130 RA cases and 260 matched controls, aged 35–70 years. Cases were identified based on biochemical tests and rheumatologist consultation.

**Outcome measures** Primary outcome was the odds of RA. Secondary outcomes included anthropometric measurements (body mass index (BMI), waist circumference) and dietary quality indicators.

**Methods** The CHLS score was calculated based on four parameters: smoking status, physical activity level, BMI and dietary quality, as assessed by the Healthy Eating Index-2020. Scores ranged from 0 (representing the unhealthiest lifestyle) to 4 (representing the healthiest lifestyle). Multiple logistic regression analysis was used to evaluate the association between CHLS and the odds of developing RA.

**Results** Participants with higher CHLS exhibited significantly lower BMI and waist circumference compared with those with lower scores. Additionally, higher CHLS was associated with greater consumption of fruits and whole grains (p<0.05). Individuals with the highest CHLS had 90% lower odds of developing RA compared with those with the lowest scores (OR 0.105; 95% CI 0.024 to 0.461, p trend=0.001), after adjusting for potential confounders.

**Conclusions** Our findings suggest that adherence to a healthy lifestyle—characterised by non-smoking, regular physical activity, maintaining a normal BMI and following a healthy dietary pattern—is associated with reduced odds of developing RA among Iranian adults. The results of this study underscore the potential importance of combined lifestyle modifications in the prevention of RA. These insights emphasise the value of promoting comprehensive lifestyle changes as a strategy to mitigate RA risk.

*   NUTRITION & DIETETICS
*   PUBLIC HEALTH
*   RHEUMATOLOGY

### STRENGTHS AND LIMITATIONS OF THIS STUDY

*   The study used a large, nationally representative database with standardised data collection protocols, which minimises potential biases.

*   A comprehensive lifestyle assessment was conducted using a validated scoring system incorporating smoking, physical activity, body mass index and dietary quality.

*   One of the limitations is that the case–control design limits our ability to establish causal relationships, and we did not evaluate stress and alcohol consumption as additional lifestyle factors in this study.

## Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by widespread inflammation, particularly affecting the joints and surrounding soft tissues.1 This condition manifests symptoms such as joint swelling, redness, pain, stiffness and general fatigue, significantly impairing the quality of life.1 Progressive disability may occur as a result of this condition, along with potential cardiovascular complications and other related health issues, as documented in various studies.1 2 RA is estimated to affect between 0.5% and 1.0% of the global population, with peak onset typically occurring between 30 and 55 years of age.3 Women are disproportionately affected by the condition, being 2–3 times more likely to develop it than men.4 The disease not only leads to chronic health issues for individuals but also imposes significant socioeconomic burdens, affecting both personal quality of life and healthcare systems. Recent data show annual healthcare costs are US$3383 higher in RA patients compared with non-RA individuals, with medication costs reaching up to US$36 000 annually.5 Literature indicates that up to 20%–30% of patients may become permanently disabled within the first 3 years of diagnosis.1 Recent epidemiological data also suggest that the prevalence of the disease is higher in Western industrialised countries compared with Eastern and developing nations.6 

RA pathogenesis is considered a complex interaction between genetic, epigenetic and environmental factors, many of which remain incompletely understood.7 However, recent epidemiological studies have highlighted the significant roles of environmental factors, microbiota, infectious agents, sex hormones and lifestyle in the development of the disease.4 8 As with other chronic diseases, modifiable lifestyle factors such as unhealthy body weight, smoking, physical inactivity and unhealthy dietary patterns significantly influence the development and progression of RA.9 Several studies suggest that, when combined, these factors may have a greater impact than when considered individually.9 The Combined Healthy Lifestyle Score (CHLS) is derived from five modifiable lifestyle factors: smoking, alcohol consumption, body mass index (BMI), physical activity and diet. These factors significantly influence not only the development of diseases but also their prognosis.10 11 

In recent years, extensive research has highlighted the central role of diet in assessing disease risk and development.6 While recent French rheumatology guidelines support Mediterranean-type diet and weight management,12 the role of fasting remains controversial. Although historic trials show fasting’s positive impact on RA activity for up to 1 year,13 14 current evidence suggests that combining fasting with a subsequent plant-based diet may be more beneficial.15 This combination can reduce inflammatory biomarkers and positively impact gut microbiota through modulation of the mTOR signalling pathway.16 17 Certain nutrients, such as polyunsaturated fatty acids (PUFAs), may function as anti-inflammatory agents and antioxidants, but substances like salt and red meat can negatively impact RA development and progression through indirect mechanisms, such as altering gut microbiota and body composition.18 High-fibre diets have been associated with improved T cell regulation and decreased bone erosion markers in RA patients,19 while adequate iron and calcium intake show positive correlations with bone health.20–22 Additionally, adequate vitamin D levels have been linked to better disease management and reduced inflammation in patients with RA.23 Furthermore, prebiotics, probiotics and synbiotics may also exert beneficial effects on RA.24 

It is well supported by substantial evidence that exercise is highly effective in treating RA in all clinical domains.2 Certain physical activities function as a non-pharmacological treatment strategy due to their numerous benefits, including enhanced muscle mass, strength and overall efficiency, particularly in patients with RA. During exercise, skeletal muscles release myokines, which exert direct anti-inflammatory effects with each activity.25 Regular physical activity has been demonstrated to reduce disease activity scores, improve joint function and promote a better quality of life among patients with RA.26 

Excess body weight appears to be another important environmental factor in the pathogenesis of RA. Obesity is associated with an increased risk of RA, which can be attributed to the secretion of adipokines from white adipose tissue. This increased risk can lead to heightened disease activity, thereby reducing the efficacy of treatment and the likelihood of achieving therapeutic targets.27 28 Studies have demonstrated that RA patients who are overweight or obese experience heightened degrees of synovial inflammation, both at the time of disease onset and after achieving remission.29 While the precise mechanisms through which obesity exerts its effects on joint damage remain multifaceted,30 the mechanical stress associated with excess weight appears to contribute to the acceleration of arthritis development in weight-bearing joints.31 Consequently, effective weight management emerges as a modifiable risk factor in the prevention and management of RA.

Smoking and alcohol have been extensively studied as environmental factors in RA. Meta-analyses show smoking significantly increases RA risk, particularly in men and antibody-positive RA (anti-citrullinated protein antibodies), with nearly 30% of RA patients being smokers.32 33 Beyond increasing risk, smoking reduces treatment efficacy, especially for anti-TNF-α drugs.34 35 The relationship between alcohol consumption and RA remains controversial. Although some studies suggest an association between alcohol consumption and antibody-positive RA through downregulation of proinflammatory cytokines,36 37 others report no significant effects on disease activity.38 Furthermore, evidence regarding alcohol’s influence on radiological damage and disease progression remains inconsistent.39 40 

Limited data exist regarding the cumulative impact of unhealthy lifestyle factors in individuals with RA.41 While several studies have assessed individual lifestyle factors, the combined effect of multiple lifestyle components on the odds of developing RA remains poorly understood.10 Recent studies on various chronic diseases have indicated that the combined impact of lifestyle factors may be more significant than the effects of individual factors.42 Additionally, preventive measures for rheumatic diseases should be implemented before individuals enter older age groups, emphasising the importance of maintaining a healthy lifestyle.25 Therefore, this study aims to investigate the significance of a CHLS in relation to RA among Iranian adults participating in the PERSIAN Dena Cohort Study (PDCS).

## Material and methods

### Participants

Data from the PDCS were used to conduct this case–control study.43 To determine the contributing factors to non-communicable diseases in Iran, researchers have been conducting the Prospective Epidemiological Research Studies in IrAN (PERSIAN) Cohort Study since 2018, using the Dena PERSIAN cohort as a subcohort. The Dena cohort includes all individuals residing in Dena County (Sisakht region) near the city of Yasuj, aged between 35 and 70, excluding those unable to participate in interviews due to physical or mental health issues. The RA status of the participants (yes or no) was determined based on the results of biochemical tests and consultations with a rheumatologist. Additional information regarding the study design, participants and data collection methods has been published previously.43 The mean values of healthy lifestyle score as a key variable were obtained from Cristina de Oliveira *et al* 44 and were used to estimate the sample size. Considering the study power of 80%, a type I error of 5%, and the ratio of controls to cases as 2, we required 130 cases and 260 controls for this study. Participants with reported daily energy intakes below 800 kcal/day or above 4500 kcal/day were excluded from the study.

### Demographic, anthropometric, supplement intake and lifestyle assessment

The data, which included demographic (age, sex, educational background, and marital status), anthropometric, medical and lifestyle measurements, were collected according to the cohort protocol by trained interviewers. Height was measured using a stadiometer (Seca 755 1021994, Germany), ensuring that participants stood against a wall with their heels and buttocks in contact. Weight was measured using a calibrated standing scale (Seca 755 1021994, Germany), with participants wearing light clothing and no shoes. BMI was calculated by dividing the weight in kilograms by the square of height in metres. According to WHO classification, overweight is defined as BMI ≥25 kg/m² and obesity as BMI ≥30 kg/m².45 Smoking status was classified according to standard definitions: non-smokers (<100 cigarettes in lifetime) and current smokers (≥100 cigarettes in lifetime and currently smoking).46 Supplement usage was defined as taking calcium and vitamin D supplements at least once a week for a minimum of 6 months. Physical activity levels were evaluated using the validated Iranian version of the International Physical Activity Questionnaire. A daily activity questionnaire was used to measure the Metabolic Equivalent (MET) for all individuals’ activities over a 24-hour period, with results expressed as MET-hour per week.47 

### Dietary assessment

In this study, a validated 113-item Food Frequency Questionnaire (FFQ) and an additional 127-item FFQ specifically designed to include indigenous foods were used.48 49 Participants reported the frequency and portion sizes of food items consumed on a daily, weekly, monthly and annual basis over the past year. All portion sizes and household quantities were converted to grams per day. The energy and nutrient content of the foods were calculated using Nutritionist IV software (V.7.0). Due to the incompleteness of the Iranian Food Composition Table (FCT), the USDA FCT was used for dietary analyses.

### Assessment of CHLS

Four lifestyle factors were used to determine the CHLS for individuals: smoking, diet quality, BMI and physical activity. Diet quality assessed by Healthy Eating Index (HEI)-2020 diet score is used to evaluate the quality of individuals’ diets. A maximum score of 100 points can be attained through the 13 components of HEI-2020, which consist of 4 moderation components and 9 adequacy components. The adequacy components—dairy, whole grains and fatty acids—received scores of 10 and 0, respectively, indicating the highest and lowest levels of intake. For the other six adequacy components, the lowest and highest intakes were 0 and 5, respectively, for total fruits (including fruit, fruit juice and canned fruit), whole fruits (excluding fruit juice), total vegetables, greens and beans, total protein foods, seafood and plant proteins. Four moderation components—salt, refined grains, saturated fats and added sugars—were assigned a maximum of 10 points for the lowest levels of consumption.50 However, the highest intake of these components was scored as 0. Finally, participants were categorised into quintiles according to their HEI-2020 scores. Individuals in the upper two quintiles were assigned a score of 1 to indicate a higher level of adherence to a healthy diet.50 The following characteristics were also assigned a score of 1: non-current smoking status, physically active or moderately active (highest and second-highest quartiles of MET-hour per week), BMI <25 kg/m2, and placement in the upper two quintiles of the Alternative Healthy Eating Index 2020 (AHEI-2020) score. To calculate the overall CHLS, we summed the participants’ scores across each lifestyle component. The scores range from 0 (indicating the lowest adherence to CHLS) to 4 (indicating the highest adherence to CHLS).51 

### Statistical analyses

The statistical analyses were performed using IBM SPSS Statistics V.25 (IBM). Statistical significance was determined by p values of less than 0.05. Qualitative variables were expressed as percentages, while quantitative variables were reported as mean±SD. The normality of continuous variables was assessed using the Kolmogorov-Smirnov test. The dietary intakes and general characteristics of the patients and controls were evaluated using the χ2 test for categorical variables and the independent samples t-test for continuous data. Additionally, one-way analysis of variance was employed to analyse continuous variables, while χ2 tests were used for categorical variables to assess the general characteristics of study participants across the categories of the CHLS. Dietary intakes of study participants across categories of the CHLS were examined using analysis of covariance, adjusting for age and sex in relation to energy intake, and further adjusting for age, sex and energy intake for all other variables. The association between the CHLS and the odds of RA was evaluated using conditional logistic regression models. In the second model, adjustments were made for age, sex, vitamin D and calcium supplement use.

### Patient and public involvement

None.

## Results

The total number of participants who entered the study was 390. Table 1 compares the general characteristics of participants between RA cases (n=130) and controls (n=260), as well as across different categories of the CHLS, which ranges from 0 to 4. While there were no significant differences in the distribution of males and females between cases and controls, significant differences were observed in their distribution across CHLS score categories. The mean BMI of RA cases was significantly higher compared with the control group (28.1±5.2 vs 26.8±4.7 kg/m², p=0.014). Furthermore, obesity, defined as a BMI ≥30 kg/m², was more prevalent among individuals with RA (33.8% vs 23.1%, p=0.023). In terms of healthy lifestyle scores, participants with a score of 0 exhibited the highest mean BMI (29.9±2.9 kg/m²), while those with a score of 4 had the lowest mean BMI (22.6±2.0 kg/m², p<0.001). Similarly, the prevalence of obesity was significantly lower among participants with a score of 4 (0%) compared with those with a score of 0 (60.0%, p<0.001). Additionally, higher waist circumference and weight were significantly associated with lower healthy lifestyle scores (p<0.001 for both). Participants with a lifestyle score of 0 exhibited the highest waist circumference (101.7±6.4 cm), whereas those with a score of 4 demonstrated the lowest waist circumference (88.9±9.4 cm, p<0.001). In this study, the difference between cases and controls was not statistically significant (97.5±12.8 cm vs 95.7±10.8 cm, p=0.141). Physical activity levels were positively associated with healthy lifestyle scores, increasing from 33.6±4.2 MET-hour/day in individuals with a score of 0 to 42.2±5.0 MET-hour/day in those with a score of 4 (p<0.001).

View this table:
[Table 1](http://bmjopen.bmj.com/content/15/3/e097715/T1)

Table 1 
General characteristics of participants by cases and controls as well as different categories of the combined healthy lifestyle score*

Table 2 highlights the dietary intake of selected nutrients and food groups among RA cases, controls and categories based on healthy lifestyle scores. Regarding energy and macronutrients, although energy intake did not differ significantly between cases and controls (p=0.191) or across CHLS categories (p=0.204), participants with a higher CHLS consumed significantly more protein (p=0.009) and fat (p=0.039). Significant differences were observed in the intake of several micronutrients across lifestyle scores. Participants with higher CHLS consumed significantly more vitamin A, vitamin C, vitamin E, zinc and magnesium compared with those with lower scores (all p<0.001). A statistically significant difference in mean vitamin B6 intakes was observed between cases and controls (13.7±0.8 mg/day vs 11.8±0.4 mg/day, p=0.030). Regarding food group consumption, individuals with a higher score of CHLS showed a significantly greater intake of fruits (p<0.001) and whole grains (p=0.038), along with a notably lower consumption of refined grains (p<0.001). Vegetable consumption was significantly lower in cases compared with controls (479±17 vs 546±26 g/day, p=0.027).

View this table:
[Table 2](http://bmjopen.bmj.com/content/15/3/e097715/T2)

Table 2 
Dietary intakes of selected nutrients and food groups of participants by cases and controls as well as different categories of the combined healthy lifestyle score*

Figure 1 illustrates the crude and multivariable-adjusted ORs for the odds of developing RA based on the CLHS. In the crude model, participants with a CLHS of 4 (the healthiest category) had significantly lower odds of developing RA compared with those with a CHLS score of 0 (OR 0.127, 95% CI 0.027 to 0.644, p-trend=0.006). After adjusting for age (continuous), sex (male/female) and the use of vitamin D and calcium supplements (yes/no), the association remained significant (OR 0.105, 95% CI 0.024 to 0.461, p-trend=0.001).

![Figure 1](http://bmjopen.bmj.com/https://bmjopen.bmj.com/content/bmjopen/15/3/e097715/F1.medium.gif)

[Figure 1](http://bmjopen.bmj.com/content/15/3/e097715/F1)

Figure 1 
Crude and multivariable-adjusted ORs with 95% CIs for the odds of rheumatoid arthritis across the different categories of the combined healthy lifestyle score (n=390). (A) Crude model; (B) Adjusted for age (continuous), sex (male/female), vitamin D and calcium supplements use (yes/no).

## Discussion

Our study, a nested case–control investigation, found a significant inverse relationship between CHLS and the likelihood of RA in Iranian adults, even after adjusting for confounders. Specifically, individuals with the highest CHLS showed a reduced the odds of RA compared with those with the lowest scores.

RA pathogenesis is multifaceted, involving genetic predispositions and environmental triggers, as well as their interactions, which play a crucial role in determining susceptibility to RA.3 Despite the strong role of genetics, numerous studies have primarily focused on single lifestyle factors, such as diet, physical activity and BMI, in relation to RA risk. However, given the interconnectivity of these lifestyle factors, considering them collectively provides a more holistic understanding of their influence on RA risk.11 52 In past studies, comprehensive lifestyle indices like the Healthy Lifestyle Index Score from the Nurses’ Health Study (NHS) have shown that maintaining multiple healthy lifestyle habits can reduce RA risk, especially in cases of seropositive RA. A recent cross-sectional study involving 17 532 adult Americans from the National Health and Nutrition Examination Survey (NHANES) cohort showed that the Life’s Simple 7 score—developed according to the American Heart Association guidelines to evaluate the cumulative effects of lifestyle risk factors for cardiovascular disease through seven indicators: blood pressure, total cholesterol, haemoglobin A1c (HbA1c), smoking, BMI, physical activity and diet exhibits a negative association with RA.42 53 Our study expands on this by focusing on a synergy between healthy diet, BMI, physical activity and smoking status as a unified CHLS and its connection to RA risk.

In terms of diet, the beneficial health effects of healthy dietary patterns have been established in relation to many chronic diseases, often by modulating levels of systemic inflammation.54 55 The role of diet in RA risk is well supported, particularly through its influence on systemic inflammation. Anti-inflammatory diets, like the AHEI-2010 and the Mediterranean diet, have demonstrated protective effects against RA. While some studies associate Mediterranean diet adherence with pain relief in RA patients, its role in preventing RA remains inconclusive.18 52 The NHS, which tracked over 150 000 women and documented more than 1000 new RA cases, found that sustained healthy eating habits were moderately linked to a lower RA risk, especially for women under 55 years.56 The study used the AHEI-2010 to evaluate dietary quality, with healthy foods—such as fruits, vegetables, whole grains, nuts, long-chain fats and PUFAs, as well as moderate alcohol use—associated with a reduced risk of chronic diseases. In contrast, higher risk was linked to consuming sugar-sweetened drinks, red and processed meats, trans fats, and foods high in sodium.18 Notably, in our study, we used the HEI-2020 to measure the nutritional quality of the diet, whereas the NHS study employed the AHEI-2010 version, which has minor differences in the scoring of dietary items. Additionally, several investigations have focused on the potential anti-inflammatory benefits of the Mediterranean diet—characterised by its abundance of fruits, vegetables, nuts, legumes, low-fat dairy, seafood, whole grains and fibre, as well as its high content of antioxidant nutrients and low levels of red and processed meat, animal fat, sweets and desserts—on the risk of RA. A systematic review assessed how the Mediterranean diet influences both the prevention and symptom management of RA in prospective studies involving humans. While findings suggested that the Mediterranean diet might help reduce pain and symptoms for individuals already diagnosed with RA, the evidence was not strong enough to confirm its role in preventing RA development.57 Another population-based case–control study involving more than 5000 participants demonstrated a significant reduction in the risk of seropositive RA among individuals with strong adherence to the Mediterranean diet; however, this effect was observed exclusively in male participants.58 These findings suggest that a generally healthy diet, as part of a healthy lifestyle, may contribute to reduced odds of RA.

Previous research has suggested various biological mechanisms by which excess body weight could affect RA risk. Obesity is known to be an inflammatory state, marked by increased levels of proinflammatory cytokines released by fat cells, such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), both of which are linked to RA development.58 59 In our study, using a BMI cut-off point of 25 kg/m2, we found that higher BMI was associated with increased odds of RA, which aligns with previous findings. On the other hand, obesity is linked to relatively higher oestrogen levels. Since RA is more common among females, this increase in oestrogen might play a role in the disease’s development and prevalence among women.60 A systematic review encompassing 11 studies explored the relationship between BMI and RA risk, finding that obesity is notably associated with a higher RA risk compared with those without obesity.61 Similarly, a later meta-analysis, which included 400 609 participants and identified 13 562 RA cases, found that obesity correlated with a relative risk of 1.21 for RA when compared with individuals with normal BMI. Additionally, for every 5 kg/m² increase in BMI, the RA risk rose by 13%.62 These findings support our results showing the importance of maintaining normal BMI (<25 kg/m²) as part of a healthy lifestyle pattern for reducing RA risk. However, these studies primarily examined BMI as a fixed category and did not assess the effects of weight or BMI fluctuations over time on RA risk.

Physical activity may contribute to the pathogenesis of RA through several mechanisms.63 These mechanisms include energy consumption, the secretion of myokines (such as IL-6, IL-8 and IL-15), modulation of T helper 1/T helper 2 (Th1/Th2) cell levels, increased levels of natural killer cells and the secretion of epinephrine and norepinephrine during exercise.64–66 Together, these effects contribute to reducing systemic inflammation, providing a rationale for the idea that physical activity may protect against RA. Findings from the Swedish Mammography Cohort, which studied 30 112 women aged 54–89 years and identified 201 new RA cases, indicated that women who engaged in higher levels of physical activity (over 20 min of walking or bicycling daily and more than 1 hour of exercise weekly) had a significantly reduced risk of developing RA compared with those in the lowest physical activity category. These findings further support the potential protective role of regular physical activity in reducing RA risk.67 Similarly, another prospective cohort study investigated the relationship between recreational physical activity and the risk of RA among women participating in the NHS II. This study used repeated measures of physical activity over 26 years and included 113 366 women, identifying 506 new cases of RA. The research focused on the correlation between levels of recreational physical activity and the risk of developing RA. The results indicated that a higher cumulative number of hours spent on recreational physical activities was associated with a significantly lower risk of developing RA compared with lower levels of physical activity. These findings underscore the potential protective effects of regular physical activity against the onset of RA, reinforcing the importance of incorporating physical activity into preventive health strategies.68 Additionally, a recent meta-analysis, comprising four studies with a total of 255 365 women and 4213 incident RA cases, identified an inverse relationship between physical activity and RA development. Notably, one study within the meta-analysis reported the progression of joint damage in large joints among individuals with existing extensive joint deterioration when engaging in high-intensity weight-bearing exercises.69 However, all studies and meta-analyses regard resistance exercise as safe and beneficial for patients with RA.70–72 Consequently, the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) both strongly recommend physical activity in RA management.26 73 EULAR recommends not only aerobic exercise but also specific muscle-strengthening exercises,26 and ACR similarly provides a strong recommendation for both types of exercise.73 Guidelines from other regions such as Asia Pacific League of Associations for Rheumatology acknowledge the potential benefits of physical activity but note that evidence and resources for structured physical therapy are limited in many countries.74 

The present study has several notable strengths. First, to the best of our knowledge, it is the first study to investigate the relationship between the combined effects of four key healthy lifestyle factors, as represented by the CHLS, and the odds of RA. Second, the study used a large, nationally representative database with standardised data collection protocols, which helps minimise potential biases. All data were collected by expert and trained interviewers using reliable and validated questionnaires. Third, the nested case–control design of this study represents a significant strength compared with cross-sectional or traditional case–control designs. This approach offers superior computational efficiency for estimating ORs while reducing the risk of selection bias and recall bias.

However, this study also has certain limitations. First, the cross-sectional nature of the data limits the ability to infer causality. Second, as an observational study, it was not possible to fully control for all potential confounding factors and biases. Although the study adjusted for several covariates, unmeasured confounding factors may still exist. Additionally, lifestyle factors were assessed only during the baseline phase of the PDCS, whereas individuals’ lifestyles are dynamic and can change over time. Fourth, despite the use of expert and trained interviewers, as well as validated questionnaires for dietary and physical activity assessments, some degree of measurement error is inevitable. These limitations should be considered when interpreting the findings, and future research should aim to address these gaps to further clarify the relationship between lifestyle factors and RA risk.

Additionally, the FFQ has several known limitations, including recall bias, seasonal variations in food intake and the potential for overestimation or underestimation of portion sizes. Fifth, due to the incompleteness of the Iranian FCT, the USDA FCT was used for dietary analyses, which may introduce minor measurement errors in the calculations of macronutrient and micronutrient intake. Furthermore, the study lacked detailed body composition measurements beyond BMI, which could have provided more precise insights into the relationship between body composition and RA risk. Finally, we did not account for additional lifestyle factors such as sleep patterns, fatigue levels, stress and alcohol consumption, despite their reported associations with RA in some studies. It is important to acknowledge that the findings of this study may not be generalisable beyond the specific sample of adults examined. Future research should aim to address these limitations to provide a more comprehensive understanding of the factors influencing RA risk.

### Conclusions

In conclusion, the results of our population-based nested case–control study indicate that individuals with a higher CHLS have significantly lower odds of developing RA, even after adjusting for potential confounders. This finding suggests an inverse association between the healthy lifestyle behaviours represented by the CHLS and the incidence of RA. However, further prospective studies with long-term follow-up are necessary to confirm the causal relationship suggested by these results. Such research would provide deeper insights into the role of lifestyle modifications in RA prevention and management.

## Data availability statement

Data are available on reasonable request. On reasonable request, the corresponding author will provide the datasets used and analysed during the current work. Correspondence and requests for materials should be addressed to M-RJ.

## Ethics statements

### Patient consent for publication

Consent obtained directly from patient(s).

### Ethics approval

This study involves human participants and the aims of the study were explained in detail, and written informed consent was obtained from all participants 20. The study was approved by the Ethics Committee of Yasuj University of Medical Sciences (ethics code: IR.YUMS.REC.1401.175). Participants gave informed consent to participate in the study before taking part.

## Acknowledgments

The authors express their gratitude to everybody who took part in the study.

## Footnotes

*   X @MrJowshan

*   Contributors Conception and design: FA, JH, M-RJ and SH-S. Acquisition of data: SA. Analysis and interpretation of data: SH-S, FA and JH. Drafting the manuscript: AP, M-AZ, FK, VM and M-RJ. Revising manuscript for intellectual content: M-RJ, SA and FA. All authors read and approved the final manuscript. M-RJ is the guarantor.

*   Funding This study was supported by Yasuj University of Medical Sciences.

*   Competing interests None declared.

*   Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

*   Provenance and peer review Not commissioned; externally peer reviewed.

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## References

1.   Di Matteo A , Bathon JM , Emery P . Rheumatoid arthritis. Lancet 2023;402:2019–33. [doi:10.1016/S0140-6736(23)01525-8](http://dx.doi.org/10.1016/S0140-6736(23)01525-8) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/S0140-6736(23)01525-8&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=38240831&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

2.   Li Z , Wang XQ . Clinical effect and biological mechanism of exercise for rheumatoid arthritis: A mini review. Front Immunol 2022;13:1089621. [doi:10.3389/fimmu.2022.1089621](http://dx.doi.org/10.3389/fimmu.2022.1089621) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=36685485&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

3.   Smolen JS , Aletaha D , McInnes IB . Rheumatoid arthritis. Lancet 2016;388:2023–38. [doi:10.1016/S0140-6736(16)30173-8](http://dx.doi.org/10.1016/S0140-6736(16)30173-8) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/s0140-6736(16)30173-8. PubMed PMID: 27156434.&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=27156434&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

4.   Venetsanopoulou AI , Alamanos Y , Voulgari PV , et al . Epidemiology of rheumatoid arthritis: genetic and environmental influences. Expert Rev Clin Immunol 2022;18:923–31. [doi:10.1080/1744666X.2022.2106970](http://dx.doi.org/10.1080/1744666X.2022.2106970) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=35904251&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

5.   Huang Y , Li J , Agarwal SK . Economic and Humanistic Burden of Rheumatoid Arthritis: Results From the US National Survey Data 2018-2020. ACR Open Rheumatol 2024;6:746–54. [doi:10.1002/acr2.11728](http://dx.doi.org/10.1002/acr2.11728) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=39105293&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

6.   Gioia C , Lucchino B , Tarsitano MG , et al . Dietary Habits and Nutrition in Rheumatoid Arthritis: Can Diet Influence Disease Development and Clinical Manifestations? Nutrients 2020;12:1456. [doi:10.3390/nu12051456](http://dx.doi.org/10.3390/nu12051456) 
    
    

7.   Lehmann J , Kyburz D . Rheumatoid Arthritis. Ther Umsch 2023;80:27–33. [doi:10.1024/0040-5930/a001403](http://dx.doi.org/10.1024/0040-5930/a001403) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=36659846&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

8.   Romão VC , Fonseca JE . Etiology and Risk Factors for Rheumatoid Arthritis: A State-of-the-Art Review. Front Med (Lausanne) 2021;8:689698. [doi:10.3389/fmed.2021.689698](http://dx.doi.org/10.3389/fmed.2021.689698) 
    
    

9.   Vajdi M , Nikniaz L , Pour Asl AM , et al . Lifestyle patterns and their nutritional, socio-demographic and psychological determinants in a community-based study: A mixed approach of latent class and factor analyses. PLoS One 2020;15:e0236242. [doi:10.1371/journal.pone.0236242](http://dx.doi.org/10.1371/journal.pone.0236242) 
    
    

10.  Hahn J , Malspeis S , Choi MY , et al . Association of Healthy Lifestyle Behaviors and the Risk of Developing Rheumatoid Arthritis Among Women. Arthritis Care Res (Hoboken) 2023;75:272–6. [doi:10.1002/acr.24862](http://dx.doi.org/10.1002/acr.24862) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=35040282&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

11.  Schäfer C , Keyßer G , Reuß-Borst M . Influence of smoking, nutrition and other modifiable environmental factors on rheumatoid arthritis. Z Rheumatol 2024;83:706–20. [doi:10.1007/s00393-024-01559-y](http://dx.doi.org/10.1007/s00393-024-01559-y) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=39158701&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

12.  Daien C , Czernichow S , Letarouilly J-G , et al . Dietary recommendations of the French Society for Rheumatology for patients with chronic inflammatory rheumatic diseases. Joint Bone Spine 2022;89:S1297-319X(21)00192-5. [doi:10.1016/j.jbspin.2021.105319](http://dx.doi.org/10.1016/j.jbspin.2021.105319) 
    
    

13.  Sköldstam L , Larsson L , Lindström FD . Effect of fasting and lactovegetarian diet on rheumatoid arthritis. Scand J Rheumatol 1979;8:249–55. [doi:10.3109/03009747909114631](http://dx.doi.org/10.3109/03009747909114631) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=534318&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 
    
    [Web of Science](http://bmjopen.bmj.com/lookup/external-ref?access_num=A1979JB96000011&link_type=ISI) 

14.  Kjeldsen-Kragh J , Haugen M , Borchgrevink CF , et al . Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet 1991;338:899–902. [doi:10.1016/0140-6736(91)91770-u](http://dx.doi.org/10.1016/0140-6736(91)91770-u) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/0140-6736(91)91770-U&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=1681264&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 
    
    [Web of Science](http://bmjopen.bmj.com/lookup/external-ref?access_num=A1991GJ89900001&link_type=ISI) 

15.  Sköldstam L . Fasting and vegan diet in rheumatoid arthritis. Scand J Rheumatol 1986;15:219–21. [doi:10.3109/03009748609102091](http://dx.doi.org/10.3109/03009748609102091) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=3749829&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 
    
    [Web of Science](http://bmjopen.bmj.com/lookup/external-ref?access_num=A1986D824900020&link_type=ISI) 

16.  Tomova A , Bukovsky I , Rembert E , et al . The Effects of Vegetarian and Vegan Diets on Gut Microbiota. Front Nutr 2019;6:47. [doi:10.3389/fnut.2019.00047](http://dx.doi.org/10.3389/fnut.2019.00047) 
    
    

17.  Aleksandrova K , Koelman L , Rodrigues CE . Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies. Redox Biol 2021;42:101869. [doi:10.1016/j.redox.2021.101869](http://dx.doi.org/10.1016/j.redox.2021.101869) 
    
    

18.  Oliviero F , Spinella P , Fiocco U , et al . How the Mediterranean diet and some of its components modulate inflammatory pathways in arthritis. Swiss Med Wkly 2015;145:w14190. [doi:10.4414/smw.2015.14190](http://dx.doi.org/10.4414/smw.2015.14190) 
    
    

19.  Häger J , Bang H , Hagen M , et al . The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study. Nutrients 2019;11:2392. [doi:10.3390/nu11102392](http://dx.doi.org/10.3390/nu11102392) 
    
    

20.  Sato H , Takai C , Kazama JJ , et al . Serum hepcidin level, iron metabolism and osteoporosis in patients with rheumatoid arthritis. Sci Rep 2020;10:9882. [doi:10.1038/s41598-020-66945-3](http://dx.doi.org/10.1038/s41598-020-66945-3) 
    
    

21.  Aizer J , Reed G , Onofrei A , et al . Predictors of bone density testing in patients with rheumatoid arthritis. Rheumatol Int 2009;29:897–905. [doi:10.1007/s00296-008-0804-4](http://dx.doi.org/10.1007/s00296-008-0804-4) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=19104820&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

22.  Oelzner P , Lehmann G , Eidner T , et al . Hypercalcemia in rheumatoid arthritis: relationship with disease activity and bone metabolism. Rheumatol Int 2006;26:908–15. [doi:10.1007/s00296-005-0095-y](http://dx.doi.org/10.1007/s00296-005-0095-y) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=16404562&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

23.  Shekhar KV , Pathak MM , Pisulkar G . Diet and Lifestyle Impact on Rheumatoid Arthritis: A Comprehensive Review. Cureus 2023;15:e48625. [doi:10.7759/cureus.48625](http://dx.doi.org/10.7759/cureus.48625) 
    
    

24.  Nelson J , Sjöblom H , Gjertsson I , et al . Do Interventions with Diet or Dietary Supplements Reduce the Disease Activity Score in Rheumatoid Arthritis? A Systematic Review of Randomized Controlled Trials. Nutrients 2020;12:2991. [doi:10.3390/nu12102991](http://dx.doi.org/10.3390/nu12102991) 
    
    

25.  Modarresi Chahardehi A , Masoumi SA , Bigdeloo M , et al . The effect of exercise on patients with rheumatoid arthritis on the modulation of inflammation. Clin Exp Rheumatol 2022;40:1420–31. [doi:10.55563/clinexprheumatol/fohyoy](http://dx.doi.org/10.55563/clinexprheumatol/fohyoy) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=34874837&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

26.  Rausch Osthoff A-K , Niedermann K , Braun J , et al . 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Ann Rheum Dis 2018;77:1251–60. [doi:10.1136/annrheumdis-2018-213585](http://dx.doi.org/10.1136/annrheumdis-2018-213585) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1136/annrheumdis-2018-213585&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=http://www.ncbi.nlm.nih.gov/pubmed/29997112&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

27.  Prasad P , Verma S , Ganguly NK , et al . Rheumatoid arthritis: advances in treatment strategies. Mol Cell Biochem 2023;478:69–88. [doi:10.1007/s11010-022-04492-3](http://dx.doi.org/10.1007/s11010-022-04492-3) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=35725992&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

28.  Moroni L , Farina N , Dagna L . Obesity and its role in the management of rheumatoid and psoriatic arthritis. Clin Rheumatol 2020;39:1039–47. [doi:10.1007/s10067-020-04963-2](http://dx.doi.org/10.1007/s10067-020-04963-2) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1007/s10067-020-04963-2&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=32016655&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

29.  Alivernini S , Tolusso B , Gigante MR , et al . Overweight/obesity affects histological features and inflammatory gene signature of synovial membrane of Rheumatoid Arthritis. Sci Rep 2019;9:10420. [doi:10.1038/s41598-019-46927-w](http://dx.doi.org/10.1038/s41598-019-46927-w) 
    
    

30.  Daïen CI , Sellam J . Obesity and inflammatory arthritis: impact on occurrence, disease characteristics and therapeutic response. RMD Open 2015;1:e000012. [doi:10.1136/rmdopen-2014-000012](http://dx.doi.org/10.1136/rmdopen-2014-000012) 
    
    

31.  Ranganath VK , Duffy EL , Garg VK , et al . Obesity Impacts Swelling of Ankle and Foot Joints in Early Rheumatoid Arthritis Patients. J Clin Rheumatol 2019;25:e8–11. [doi:10.1097/RHU.0000000000000799](http://dx.doi.org/10.1097/RHU.0000000000000799) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=29683839&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

32.  Jamal A , King BA , Neff LJ , et al . Current Cigarette Smoking Among Adults - United States, 2005-2015. MMWR Morb Mortal Wkly Rep 2016;65:1205–11. [doi:10.15585/mmwr.mm6544a2](http://dx.doi.org/10.15585/mmwr.mm6544a2) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.15585/mmwr.mm6544a2&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=27832052&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

33.  McClave AK , Whitney N , Thorne SL , et al . Adult tobacco survey-19 States, 2003-2007. Morb Mortal Wkly Rep Surveill Summ 2002;59:1–75.
    
    

34.  Taylor PC , Matucci Cerinic M , Alten R , et al . Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: optimising treatment outcomes. Ther Adv Musculoskelet Dis 2022;14:1759720X221114101. [doi:10.1177/1759720X221114101](http://dx.doi.org/10.1177/1759720X221114101) 
    
    

35.  Vittecoq O , Richard L , Banse C , et al . The impact of smoking on rheumatoid arthritis outcomes. Joint Bone Spine 2018;85:135–8. [doi:10.1016/j.jbspin.2017.12.004](http://dx.doi.org/10.1016/j.jbspin.2017.12.004) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/j.jbspin.2017.12.004&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=29246527&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

36.  Källberg H , Jacobsen S , Bengtsson C , et al . Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case-control studies. Ann Rheum Dis 2009;68:222–7. [doi:10.1136/ard.2007.086314](http://dx.doi.org/10.1136/ard.2007.086314) 
    
    [Abstract/FREE Full Text](http://bmjopen.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTE6ImFubnJoZXVtZGlzIjtzOjU6InJlc2lkIjtzOjg6IjY4LzIvMjIyIjtzOjQ6ImF0b20iO3M6MjY6Ii9ibWpvcGVuLzE1LzMvZTA5NzcxNS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

37.  Morris NL , Ippolito JA , Curtis BJ , et al . Alcohol and inflammatory responses: summary of the 2013 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 2015;49:1–6. [doi:10.1016/j.alcohol.2014.07.018](http://dx.doi.org/10.1016/j.alcohol.2014.07.018) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/j.alcohol.2014.07.018&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=25468277&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

38.  Baker JF , England BR , Mikuls TR , et al . Changes in Alcohol Use and Associations With Disease Activity, Health Status, and Mortality in Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 2020;72:301–8. [doi:10.1002/acr.23847](http://dx.doi.org/10.1002/acr.23847) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=30891938&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

39.  Maxwell JR , Gowers IR , Moore DJ , et al . Alcohol consumption is inversely associated with risk and severity of rheumatoid arthritis. Rheumatology (Sunnyvale) 2010;49:2140–6. [doi:10.1093/rheumatology/keq202](http://dx.doi.org/10.1093/rheumatology/keq202) 
    
    

40.  Bergman S , Symeonidou S , Andersson ML , et al . Alcohol consumption is associated with lower self-reported disease activity and better health-related quality of life in female rheumatoid arthritis patients in Sweden: data from BARFOT, a multicenter study on early RA. BMC Musculoskelet Disord 2013;14:218. [doi:10.1186/1471-2474-14-218](http://dx.doi.org/10.1186/1471-2474-14-218) 
    
    

41.  Karstensen JK , Primdahl J , Andersson MLE , et al . Lifestyle factors in patients with rheumatoid arthritis-a cross-sectional study on two Scandinavian cohorts. Clin Rheumatol 2022;41:387–98. [doi:10.1007/s10067-021-05905-2](http://dx.doi.org/10.1007/s10067-021-05905-2) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=34505213&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

42.  Wang J , Xing F , Sheng N , et al . Association between Life’s simple 7 and rheumatoid arthritis in adult Americans: data from the National Health and nutrition examination survey. Front Public Health 2023;11:1251002. [doi:10.3389/fpubh.2023.1251002](http://dx.doi.org/10.3389/fpubh.2023.1251002) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=38094235&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

43.  Harooni J , Joukar F , Goujani R , et al . Cohort profile: the PERSIAN Dena Cohort Study (PDCS) of non-communicable diseases in Southwest Iran. BMJ Open 2024;14:e079697. [doi:10.1136/bmjopen-2023-079697](http://dx.doi.org/10.1136/bmjopen-2023-079697) 
    
    

44.  Cristina de Oliveira N , Alfieri FM , Lima ARS , et al . Lifestyle and Pain in Women With Knee Osteoarthritis. Am J Lifestyle Med 2019;13:606–10. [doi:10.1177/1559827617722112](http://dx.doi.org/10.1177/1559827617722112) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=31662727&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

45. World Health Organization. Obesity: preventing and managing the global epidemic: report of a WHO consultation. 2000.
    
    

46. Control CfD, Prevention. Cigarette smoking among adults--United States, 2004. MMWR 2005;54:1121–4.
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=16280969&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

47.  Moghaddam MB , Aghdam FB , Jafarabadi MA , et al . The Iranian Version of International Physical Activity Questionnaire (IPAQ) in Iran: content and construct validity, factor structure, internal consistency and stability. World Appl Sci J 2012;18:1073–80.
    
    

48.  Eghtesad S , Masoudi S , Sharafkhah M , et al . Validity and reproducibility of the PERSIAN Cohort food frequency questionnaire: assessment of major dietary patterns. Nutr J 2024;23:35. [doi:10.1186/s12937-024-00938-0](http://dx.doi.org/10.1186/s12937-024-00938-0) 
    
    

49.  Eghtesad S , Hekmatdoost A , Faramarzi E , et al . Validity and reproducibility of a food frequency questionnaire assessing food group intake in the PERSIAN Cohort Study. Front Nutr 2023;10:1059870. [doi:10.3389/fnut.2023.1059870](http://dx.doi.org/10.3389/fnut.2023.1059870) 
    
    

50.  Shams-White MM , Pannucci TE , Lerman JL , et al . Healthy Eating Index-2020: Review and Update Process to Reflect the Dietary Guidelines for Americans,2020-2025. J Acad Nutr Diet 2023;123:1280–8. [doi:10.1016/j.jand.2023.05.015](http://dx.doi.org/10.1016/j.jand.2023.05.015) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=37201748&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

51.  Ebrahimpour-Koujan S , Shayanfar M , Mohammad-Shirazi M , et al . A combined healthy lifestyle score in relation to glioma: a case-control study. Nutr J 2022;21:6. [doi:10.1186/s12937-022-00758-0](http://dx.doi.org/10.1186/s12937-022-00758-0) 
    
    

52.  Zaccardelli A , Friedlander HM , Ford JA , et al . Potential of Lifestyle Changes for Reducing the Risk of Developing Rheumatoid Arthritis: Is an Ounce of Prevention Worth a Pound of Cure? Clin Ther 2019;41:1323–45. [doi:10.1016/j.clinthera.2019.04.021](http://dx.doi.org/10.1016/j.clinthera.2019.04.021) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/j.clinthera.2019.04.021&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=31196646&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

53.  Lin MP , Ovbiagele B , Markovic D , et al . “Life’s Simple 7” and Long-Term Mortality After Stroke. J Am Heart Assoc 2015;4:e001470. [doi:10.1161/JAHA.114.001470](http://dx.doi.org/10.1161/JAHA.114.001470) 
    
    

54.  Giugliano D , Ceriello A , Esposito K . The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol 2006;48:677–85. [doi:10.1016/j.jacc.2006.03.052](http://dx.doi.org/10.1016/j.jacc.2006.03.052) 
    
    [FREE Full Text](http://bmjopen.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6MzoiUERGIjtzOjExOiJqb3VybmFsQ29kZSI7czo0OiJhY2NqIjtzOjU6InJlc2lkIjtzOjg6IjQ4LzQvNjc3IjtzOjQ6ImF0b20iO3M6MjY6Ii9ibWpvcGVuLzE1LzMvZTA5NzcxNS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

55.  Hu FB . Dietary pattern analysis: a new direction in nutritional epidemiology. Curr Opin Lipidol 2002;13:3–9. [doi:10.1097/00041433-200202000-00002](http://dx.doi.org/10.1097/00041433-200202000-00002) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1097/00041433-200202000-00002&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=11790957&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 
    
    [Web of Science](http://bmjopen.bmj.com/lookup/external-ref?access_num=000174080900002&link_type=ISI) 

56.  Hu Y , Sparks JA , Malspeis S , et al . Long-term dietary quality and risk of developing rheumatoid arthritis in women. Ann Rheum Dis 2017;76:1357–64. [doi:10.1136/annrheumdis-2016-210431](http://dx.doi.org/10.1136/annrheumdis-2016-210431) 
    
    [Abstract/FREE Full Text](http://bmjopen.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTE6ImFubnJoZXVtZGlzIjtzOjU6InJlc2lkIjtzOjk6Ijc2LzgvMTM1NyI7czo0OiJhdG9tIjtzOjI2OiIvYm1qb3Blbi8xNS8zL2UwOTc3MTUuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

57.  Forsyth C , Kouvari M , D’Cunha NM , et al . The effects of the Mediterranean diet on rheumatoid arthritis prevention and treatment: a systematic review of human prospective studies. Rheumatol Int 2018;38:737–47. [doi:10.1007/s00296-017-3912-1](http://dx.doi.org/10.1007/s00296-017-3912-1) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

58.  Johansson K , Askling J , Alfredsson L , et al . Mediterranean diet and risk of rheumatoid arthritis: a population-based case-control study. Arthritis Res Ther 2018;20:175. [doi:10.1186/s13075-018-1680-2](http://dx.doi.org/10.1186/s13075-018-1680-2) 
    
    

59.  Van Raemdonck K , Umar S , Szekanecz Z , et al . Impact of obesity on autoimmune arthritis and its cardiovascular complications. Autoimmun Rev 2018;17:821–35. [doi:10.1016/j.autrev.2018.02.007](http://dx.doi.org/10.1016/j.autrev.2018.02.007) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=29885537&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

60.  McTiernan A , Wu L , Chen C , et al . Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring) 2006;14:1662–77. [doi:10.1038/oby.2006.191](http://dx.doi.org/10.1038/oby.2006.191) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1038/oby.2006.191&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=17030978&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

61.  Qin B , Yang M , Fu H , et al . Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis. Arthritis Res Ther 2015;17:86. [doi:10.1186/s13075-015-0601-x](http://dx.doi.org/10.1186/s13075-015-0601-x) 
    
    

62.  Feng J , Chen Q , Yu F , et al . Body Mass Index and Risk of Rheumatoid Arthritis: A Meta-Analysis of Observational Studies. Medicine (Baltimore) 2016;95:e2859. [doi:10.1097/MD.0000000000002859](http://dx.doi.org/10.1097/MD.0000000000002859) 
    
    

63.  Sharif K , Watad A , Bragazzi NL , et al . Physical activity and autoimmune diseases: Get moving and manage the disease. Autoimmun Rev 2018;17:53–72. [doi:10.1016/j.autrev.2017.11.010](http://dx.doi.org/10.1016/j.autrev.2017.11.010) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/j.autrev.2017.11.010&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

64.  Díaz BB , González DA , Gannar F , et al . Myokines, physical activity, insulin resistance and autoimmune diseases. Immunol Lett 2018;203:1–5. [doi:10.1016/j.imlet.2018.09.002](http://dx.doi.org/10.1016/j.imlet.2018.09.002) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/j.imlet.2018.09.002&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=30194964&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

65.  Pedersen BK , Fischer CP . Beneficial health effects of exercise--the role of IL-6 as a myokine. Trends Pharmacol Sci 2007;28:152–6. [doi:10.1016/j.tips.2007.02.002](http://dx.doi.org/10.1016/j.tips.2007.02.002) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/j.tips.2007.02.002&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=17331593&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

66.  Nielsen S , Pedersen BK . Skeletal muscle as an immunogenic organ. Curr Opin Pharmacol 2008;8:346–51. [doi:10.1016/j.coph.2008.02.005](http://dx.doi.org/10.1016/j.coph.2008.02.005) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1016/j.coph.2008.02.005&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=18417420&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 
    
    [Web of Science](http://bmjopen.bmj.com/lookup/external-ref?access_num=000257120500020&link_type=ISI) 

67.  Di Giuseppe D , Bottai M , Askling J , et al . Physical activity and risk of rheumatoid arthritis in women: a population-based prospective study. Arthritis Res Ther 2015;17:40. [doi:10.1186/s13075-015-0560-2](http://dx.doi.org/10.1186/s13075-015-0560-2) 
    
    

68.  Liu X , Tedeschi SK , Lu B , et al . Long-Term Physical Activity and Subsequent Risk for Rheumatoid Arthritis Among Women: A Prospective Cohort Study. Arthritis Rheumatol 2019;71:1460–71. [doi:10.1002/art.40899](http://dx.doi.org/10.1002/art.40899) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=30920773&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 

69.  Munneke M , de Jong Z , Zwinderman AH , et al . Effect of a high-intensity weight-bearing exercise program on radiologic damage progression of the large joints in subgroups of patients with rheumatoid arthritis. Arthritis Rheum 2005;53:410–7. [doi:10.1002/art.21165](http://dx.doi.org/10.1002/art.21165) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1002/art.21165&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=15934121&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 
    
    [Web of Science](http://bmjopen.bmj.com/lookup/external-ref?access_num=000229651500016&link_type=ISI) 

70.  Rausch Osthoff A-K , Juhl CB , Knittle K , et al . Effects of exercise and physical activity promotion: meta-analysis informing the 2018 EULAR recommendations for physical activity in people with rheumatoid arthritis, spondyloarthritis and hip/knee osteoarthritis. RMD Open 2018;4:e000713. [doi:10.1136/rmdopen-2018-000713](http://dx.doi.org/10.1136/rmdopen-2018-000713) 
    
    

71.  Baillet A , Vaillant M , Guinot M , et al . Efficacy of resistance exercises in rheumatoid arthritis: meta-analysis of randomized controlled trials. Rheumatology (Oxford) 2012;51:519–27. [doi:10.1093/rheumatology/ker330](http://dx.doi.org/10.1093/rheumatology/ker330) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1093/rheumatology/ker330&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=22120463&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom) 
    
    [Web of Science](http://bmjopen.bmj.com/lookup/external-ref?access_num=000300789000017&link_type=ISI) 

72.  Sveaas SH , Smedslund G , Hagen KB , et al . Effect of cardiorespiratory and strength exercises on disease activity in patients with inflammatory rheumatic diseases: a systematic review and meta-analysis. Br J Sports Med 2017;51:1065–72. [doi:10.1136/bjsports-2016-097149](http://dx.doi.org/10.1136/bjsports-2016-097149) 
    
    [Abstract/FREE Full Text](http://bmjopen.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiYmpzcG9ydHMiO3M6NToicmVzaWQiO3M6MTA6IjUxLzE0LzEwNjUiO3M6NDoiYXRvbSI7czoyNjoiL2Jtam9wZW4vMTUvMy9lMDk3NzE1LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

73.  England BR , Smith BJ , Baker NA , et al . American College of Rheumatology Guideline for exercise, rehabilitation, diet, and additional integrative interventions for rheumatoid arthritis. Arthritis Rheumatol 2022;75:1299–311.
    
    

74.  Lau CS , Chia F , Harrison A , et al . APLAR rheumatoid arthritis treatment recommendations. Int J Rheum Dis 2015;18:685–713. [doi:10.1111/1756-185X.12754](http://dx.doi.org/10.1111/1756-185X.12754) 
    
    [CrossRef](http://bmjopen.bmj.com/lookup/external-ref?access_num=10.1111/1756-185X.12754&link_type=DOI) 
    
    [PubMed](http://bmjopen.bmj.com/lookup/external-ref?access_num=26334449&link_type=MED&atom=%2Fbmjopen%2F15%2F3%2Fe097715.atom)