Smoking, gender and rheumatoid arthritis–epidemiological clues to etiology: Results from the behavioral risk factor surveillance system

doi:10.1016/S1297-319X(03)00141-6

Joint Bone Spine

Volume 70, Issue 6, December 2003, Pages 496-502

https://doi.org/10.1016/S1297-319X(03)00141-6 Get rights and content

Abstract

Objective.– This study was undertaken to confirm and extend our earlier observation that gender is a biological effect modifier of smoking–rheumatoid arthritis (RA) relationship in a diverse national survey sample in the United States.

Methods.– Smoking history of 644 cases of RA and 1509 geographically matched general population controls were compared using weighted logistic regression.

Results.– There were 644 respondents with RA (cases) and 1509 geographically matched controls. Cases were significantly younger, less educated, more likely to be single and female than controls. Among cases 57% were smokers while among controls 49% smoked. Among women, after adjusting for age, hysterectomy had an age adjusted odds ratio 1.45, (95% CI 0.99–2.10) and menopause an adjusted odds ratio 1.18 (95% CI 0.99–2.10) were associated with smoking. In univariable analysis ever-smoking was associated with increased risk of RA (odds ratio 1.34, 95% CI 1.0–1.81). Among the strata of smokers, there was an increasing gradient of risk with increasing exposure to smoking (P = 0.041). In separate multivariable models, smoking increased the risk in men (odds ratio 2.29, 95% CI 1.35–3.90) while in women the risk was not elevated (odds ratio 0.98, 95% CI 0.67–1.42). After adjusting for the statistically significant interaction both female gender (odds ratio 2.30, 95% CI 1.39–3.83) and having ever smoked (odds ratio 2.31, 95% CI 1.36–3.94) emerged as significant risk factors for RA.

Conclusions.– Gender interacts with smoking in by an unknown mechanism to lead to differential risk of RA.

Introduction

Smoking is known to be associated with production of rheumatoid factor [1], [2], [3]; rheumatoid factor production, in turn, often precedes development of clinical rheumatoid arthritis (RA) [3], [4]. Although epidemiological studies have suggested that smoking leads to increased risk of RA in men [5], [6], few studies have focused on the interaction between smoking and gender in the pathogenesis of RA. Recently our group formally presented a case for such an interaction and proposed that gender specific factors, especially menstruation may modify the immunological milieu resulting in some form of “protection” for women. If this hypothesis is true, such an effect should be observable in diverse populations. We used data from the behavioral risk factor surveillance system (BRFSS), an ongoing state-based survey in the United States to test the hypothesis that gender acts as a biologic effect-modifier in the smoking–RA association.

Section snippets

Data collection

The BRFSS is a collaborative project of the centers for disease control and prevention (CDC), and US states and territories. The BRFSS, administered and supported by the Behavioral Surveillance Branch of the CDC, is an on-going data collection program designed to measure behavioral risk factors in the adult population 18 years of age or over living in households. Random digit dialing is used to select households and within each household, one adult is randomly selected for a computer assisted

Socio-demographic variables

We identified a total of 644 persons with RA (cases) and 1509 persons with no joint symptoms (controls). Fig. 1 illustrates the age distribution of cases and controls. Table 1 shows the comparison between the socio-demographic and smoking characteristics of cases and controls. Cases were more likely than controls to be younger, female, less well educated, of lower annual income, obese, and living alone.

Smoking

Overall, cases were more likely than controls to report having ever smoked (57 vs. 49%, P

Discussion

The results of our study substantiate our earlier report and hypothesis that gender is an effect modifier of smoking–RA relationship [16]. Our observation of the relationship between smoking and the risk of RA is in line with previous population based case-control [6], [17], [18], [19], cohort [5], [20], [21], [22], [23] and twin studies [24]. Our risk estimates for men and women are consistent with the previous studies [5], [6]. Among studies done on women-only cohorts, the presence of

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Male rheumatoid arthritis patients at substantially higher risk for cardiovascular mortality in comparison to women
2023, Seminars in Arthritis and Rheumatism
Patients with rheumatoid arthritis (RA) are at an increased risk for developing cardiovascular diseases. While advice regarding cardiovascular risk screening and management in RA patients has been incorporated in several guidelines in recent years, its implementation and adherence is still poor.
To assess the cardiovascular disease risk in new diagnosed RA patients and evaluate whether advice to initiate preventive medical treatment of high risk patients was followed.
All patients with a recent diagnosis of RA, aged 40–70 years, were screened between May 2019 and December 2022 for cardiovascular diseases and risk factors within the first year after diagnosis at the outpatient rheumatology clinic, as part of standard care. Screening included a physical examination with blood pressure measurement, and laboratory tests with lipid profile tests. All patients and their general practitioner (GP) received an overview with their cardiovascular risk profile and a calculated 10-year cardiovascular mortality risk. Cardiovascular risk was defined as low (<1%), intermediate (1–5%), high (5–10%) and very high (>10%). The national pharmacy network was consulted to check whether or not patients started preventive medication after screening.
A total of 125 RA patients was included in this study. The mean age was 56 years and 78% was female. Median RA disease duration at screening was 6 months. Six patients (5%) indicated to have been screened before, and used antihypertensive medication. During screening, hypertension was found in 57% of male patients and 43% of female patients and dyslipidemia was found in 36% in male and 32% in female patients. 46% of male patients and 21% of female patients currently smoked. A high or very high 10-year cardiovascular mortality risk was found in 50% of male patients, but in only 4% of female patients. Only 26% of (very) high risk patients started antihypertensive or statin medication after screening.
An increased cardiovascular disease risk is often present in newly diagnosed RA patients, especially male patients, with a large proportion having undiagnosed and untreated hypertension and hypercholesterolemia. Even with structural screening and informing of the patients and GPs, treatment of cardiovascular risk factors in high risk patients remains insufficient. CV risk screening needs to be part of standard care for RA patients, with clear agreement on the responsibilities between primary and secondary care. Awareness of the importance of CVD risk screening needs to improve among both RA patients themselves and the GPs to ultimately reduce the cardiovascular burden of our patients. Obviously, a better collaboration between GPs and rheumatologists is urgently needed to lower the cardiovascular burden of our patients.
The association between smoking and the development of rheumatoid arthritis: a population-based case-control study
2021, Reumatologia Clinica
Smoking is one of the few modifiable risk factors associated with the development of rheumatoid arthritis (RA). Most published data are over 10 years old, and none included Mediterranean populations. We therefore took advantage of primary care routinely collected data to study the association between smoking and the development of RA in the general population of Catalonia, Spain.
We conducted a case–control study including all patients with a new diagnosis of RA registered in the SIDIAP database between 01/01/2008 and 31/12/2018; and matched them to up to 1:5 controls by age, gender and general practitioner. Smoking was classified by primary care staff into never, ex- or current smoking. Odds Ratios and 95% confidence intervals for the association between current and ex-smoking (compared to never smoking) and RA were estimated using conditional logistic regression adjusted for potential confounders.
A total of 13,920 RA cases and 69,535 controls were included. Compared with never smokers, current and ex-smokers were at increased risk of RA, with adjusted OR of 1.28 [95% CI 1.20–1.37] and OR 1.19 [1.12–1.26] respectively.
Our findings confirm an association between smoking and the risk of developing RA. The effect seems to prevail in the long-term and even in ex-smokers for 2 or more years after smoking cessation. More research is needed on the effects of smoking discontinuation on RA prevention and related outcomes.
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Realizamos un estudio de casos y controles, incluyendo a todos los pacientes con diagnóstico reciente de AR, registrados en la base de datos SIDIAP entre el 1 de enero de 2008 y el 31 de diciembre de 2018, y los pareamos con hasta 1:5 controles por edad, sexo y médico general. El tabaquismo fue clasificado por el personal de atención primaria como: no fumador, ex fumador, o fumador actual. Se calcularon los odds ratios y los intervalos de confianza del 95% para la asociación entre fumador actual y ex fumador (en comparación con no fumador) y AR, utilizando una regresión logística condicional ajustada a los factores potenciales de confusión.
Se incluyó un total de 13.920 casos de AR y 69.535 controles. En comparación con los no fumadores, los fumadores actuales y los ex fumadores tuvieron un riesgo incrementado de AR, con un OR ajustado de 1,28 [95% IC de 1,20 a 1,37] y OR 1,19 [de 1,12 a 1,26], respectivamente.
Nuestros hallazgos confirman la asociación entre tabaquismo y riesgo de desarrollo de AR. El efecto parece prevalecer a largo plazo, incluso en ex fumadores durante 2 o más años, tras haber dejado de fumar. Son necesarios más estudios sobre los efectos que tiene el dejar de fumar en la prevención de AR y los resultados conexos.
Noninfectious environmental agents and autoimmunity
2019, The Autoimmune Diseases
Autoimmune diseases appear to be increasing throughout the world, yet their rarity, heterogeneity and complex etiologies have limited our understanding of their pathogeneses. While the precise mechanisms for the development of autoimmune diseases are not known, evidence from many complementary lines of research suggests that autoimmune diseases result from the interactions of both environmental and genetic risk factors, in the context of the relative absence of protective factors. Considerable progress has been made in understanding the multiple and sometimes shared genetic risk factors for many autoimmune diseases, however, relatively little information has been collected regarding the role of the environment in the development of these illnesses. Here we examine the challenges in defining environmental risk and protective factors for disease, the limited but growing evidence for the role of noninfectious environmental exposures in the development and progression of autoimmune diseases, the specific exposures that have been suspected of being involved, the possible mechanisms by which these agents may induce and sustain autoimmune processes, and the approaches needed to better understand these issues in the future. Identifying the necessary and sufficient genetic and environmental risk and protective factors for disease phenotypes may eventually allow for the prevention of some illnesses. This could be accomplished through avoidance of environmental risk factors or by enhancing exposure to protective factors in genetically susceptible individuals, or via gene or other therapies to correct the effects of deleterious genetic risk factors in the case of unavoidable environmental risk agents. More efforts need to be dedicated to identify such risk and protective factors given the clinical and financial importance of the prevention of autoimmune disease in the future.
Non-infectious Environmental Agents and Autoimmunity
2013, The Autoimmune Diseases: Fifth Edition
Autoimmune diseases appear to be rapidly increasing in recognition throughout the world, yet the precise mechanisms for their development remain unclear. Evidence from several lines of investigation, however, implies that they develop after the interactions of both environmental and genetic risk factors. Compared to the genetic data available, relatively little information has been generated to allow understanding of the role of environment agents in the development of autoimmunity. Here, the specific drugs, biologic agents, occupational, chemical, and other non-infectious exposures that have been suspected of being involved, the possible mechanisms by which these agents may induce and sustain autoimmune processes, and the approaches needed to better understand these issues in the future are reviewed. Defining the necessary and sufficient environmental and genetic risk factors for autoimmunity could allow for the prevention of some illnesses in the future through avoidance of environmental risk factors by genetically susceptible individuals.
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2013, Clinical Imaging: With Skeletal, Chest, & Abdominal Pattern Differentials: Third Edition
Tobacco and other environmental risk factors in rheumatoid arthritis
2012, Reumatologia Clinica
Existen distintos factores ambientales implicados en la patogenia de la artritis reumatoide, aunque es el tabaco el factor más ampliamente estudiado y reconocido. El tabaquismo está asociado a un incremento del riesgo de artritis reumatoide seropositiva (FR y/o ACPA). Además estudios recientes ponen de manifiesto que el consumo de tabaco puede influir en la expresión clínica de la enfermedad, determinar un curso evolutivo más grave y una mayor destrucción articular, aunque no todos los estudios son concordantes. Datos recientes sugieren que la respuesta al tratamiento antirreumático sería peor en los enfermos fumadores. En el presente artículo se revisan los distintos factores ambientales que han sido implicados en la AR, con especial énfasis en el tabaquismo.
Many environmental factors have been associated with an increased risk of developing Rheumatoid Arthritis (RA), but so far smoking is the only environmental risk factor that has been extensively studied and widely accepted. Smoking is associated with an increased risk of developing seropositive RA (RF and/or ACPA). Recent studies show that tobacco smoking can influence disease phenotype, with the development of more aggressive disease and greater joint damage; but other studies show contradictory results. Recent data suggests that response to antirheumatic therapy in RA is worse in smokers. In this article we review different environmental factors that have been associated with an increased risk of developing RA, with a special interest in tobacco smoking.

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^☆: This data was presented as a poster in the 65th Annual Scientific Meeting of the American College of Rheumatology at San Francisco, October 2001.

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Original articleSmoking, gender and rheumatoid arthritis–epidemiological clues to etiology: Results from the behavioral risk factor surveillance system☆

Abstract

Introduction

Section snippets

Data collection

Socio-demographic variables

Smoking

Discussion

Semin Arthritis Rheum

Am J Prev M

Am J Prev M

Am J Prev M

Am J M

Contraception

Semin Arthritis Rheum

Lancet

Does smoking stimulate rheumatoid factor production in non-rheumatic individuals?

APMIS

Smoking, lung function, and rheumatoid factors

Ann Rheum Dis

Rheumatoid factors antedating clinical rheumatoid arthritis

J Rheumatol

Smoking and risk of rheumatoid arthritis

J Rheumatol

Current tobacco smoking, formal education, and the risk of rheumatoid arthritis

J Rheumatol

dm46: enhancement to the sample command

Stata Technical Bull

Reliability of information on chronic disease risk factors collected in the Missouri Behavioral Risk Factor Surveillance System

Epidemiology

STATA program. Version 7.0

Original article
Smoking, gender and rheumatoid arthritis–epidemiological clues to etiology: Results from the behavioral risk factor surveillance system☆